Research Article
BibTex RIS Cite

Year 2025, Volume: 29 Issue: 4, 1693 - 1711, 05.07.2025

Zeynep Erik İshak Erik Can Özgür Yalçın , Sıla Özlem Sener , Şengül Alpay Karaoğlu , Gizem Tatar , Nurettin Yaylı , Rezzan Aliyazıcıoğlu

https://doi.org/10.12991/jrespharm.1734661

Abstract

References

  • [1]Rammohan A, Reddy JS, Sravya G, Rao CN, Zyryanov GV. Chalcone synthesis, properties and medicinal applications: a review. Environ Chem Lett. 2020; 18(2): 433-458. https://doi.org/10.1007/s10311-019-00959-w.
  • [2]Rudrapal M, Khan J, Dukhyil AAB, Alarousy RMII, Attah EI, Sharma T, Khairnar SJ, Bendale AR. (Chalcone scaffolds, bioprecursors of flavonoids: Chemistry, bioactivities, and pharmacokinetics. Molecules. 2021; 26(23): 7177. https://doi.org/10.3390/molecules26237177.
  • [3]Gaonkar SL and Vignesh U. Synthesis and pharmacological properties of chalcones: A review. Res Chem Intermediat. 2017; 43(11): 6043-6077. https://doi.org/10.1007/s11164-017-2977-5.
  • [4]Ouyang Y, Li J, Chen X, Fu X, Sun S, Wu Q. Chalcone derivatives: role in anticancer therapy. Biomolecules. 2021; 11(6): 894. https://doi.org/10.3390/biom11060894.
  • [5]Sahu N, Balbhadra S, Choudhary J, Kohli D. Exploring pharmacological significance of chalcone scaffold: A review. Curr Med Chem. 2012; 19(2): 209-225. https://doi.org/10.2174/092986712803414132.
  • [6]Romagnoli R, Baraldi PG, Carrion MD, Cruz-Lopez O, Cara CL, Balzarini J, Hamel E, Canella A, Fabbri E, Gambari R. Hybrid ƒ¿-bromoacryloylamido chalcones. Design, synthesis and biological evaluation Bioorg Med Chem Lett. 2009; 19(7): 2022-2028. https://doi.org/10.1016/j.bmcl.2009.02.038.
  • [7]Sharma A, Chakravarti B, Gupt MP, Siddiqui JA, Konwar R, Tripathi RP. Synthesis and anti breast cancer activity of biphenyl based chalcones. Bioorg Med Chem. 2010; 18(13): 4711-4720. https://doi.org/10.1016/j.bmc.2010.05.015.
  • [8]Saunders KH, Umashanker D, Igel LI, Kumar RB, Aronne LJ. Obesity pharmacotherapy. Med Clin. 2018; 102(1): 135-148. https://doi.org/10.1016/j.mcna.2017.08.010.
  • [9]Akter N, Qureshi NK, Ferdous HS. Obesity: a review of pathogenesis and management strategies in adult. Delta Med Coll J. 2017; 5(1): 35-48. https://doi.org/10.3329/dmcj.v5i1.31436.
  • [10]Watanabe H, Saji H, Ono M. Novel fluorescence probes based on the chalcone scaffold for in vitro staining of ƒÀ-amyloid plaques. Bioorg Med Chem Lett. 2018; 28(19): 3242-3246. https://doi.org/10.1016/j.bmcl.2018.08.009.
  • [11]Nagai H, He JX, Tani T, Akao T. Antispasmodic activity of licochalcone A, a species]specific ingredient of Glycyrrhiza inflata roots. J Pharm Pharmacol. 2007; 59(10): 1421-1426. https://doi.org/10.1211/jpp.59.10.0013.
  • [12]Nazarian Z, Emami S, Heydari S, Ardestani SK, Nakhjiri M, Poorrajab F, Shafiee A, Foroumadi A. Novel antileishmanial chalconoids: Synthesis and biological activity of 1-or 3-(6-chloro-2H-chromen-3-yl) propen-1-ones. Eur J Med Chem. 2010; 45(4): 1424-1429. https://doi.org/10.1016/j.ejmech.2009.12.046
  • [13]Mahapatra DK, Asati V, Bharti SK. Chalcones and their therapeutic targets for the management of diabetes: structural and pharmacological perspectives. Eur J Med Chem. 2015; 92: 839-865. https://doi.org/10.1016/j.ejmech.2015.01.051.
  • [14]Damazio RG, Zanatta AP, Cazarolli LH, Chiaradia LD, Mascarello A, Nunes RJ, Yunes RA, Silva FRMB. Antihyperglycemic activity of naphthylchalcones. Eur J Med Chem. 2010; 45(4): 1332-1337. https://doi.org/10.1016/j.ejmech.2009.12.017.
  • [15]Sashidhara KV, Kumar M, Modukuri RK, Sonkar R, Bhatia G, Khanna A, Rai S, Shukla R. Synthesis and anti-inflammatory activity of novel biscoumarin–chalcone hybrids. Bioorg Med Chem Lett. 2011; 21(15): 4480-4484. https://doi.org/10.1016/j.bmcl.2011.06.002.
  • [16]Singh AK, Singh R. Pharmacotherapy in obesity: A systematic review and meta-analysis of randomized controlled trials of anti-obesity drugs. Expert Rev Clin Pharmacol. 2020; 13(1): 53-64. https://doi.org/10.1080/17512433.2020.1698291.
  • [17]Berhane HY, Jirström M, Abdelmenan S, Berhane Y, Alsanius B, Trenholm J, Ekström E-C. Social stratification, diet diversity and malnutrition among preschoolers: a survey of Addis Ababa, Ethiopia. Nutrients. 2020; 12(3): 712. https://doi.org/10.3390/nu12030712.
  • [18]Toader C, Tataru CP, Munteanu O, Serban M, Covache-Busuioc RA, Ciurea AV, Enyedi M. Decoding Neurodegeneration: A review of molecular mechanisms and therapeutic advances in Alzheimer's, Parkinson's, and ALS. Int J Mol Sci. 2024; 25(23): 12613. https://doi.org/10.3390/ijms252312613.
  • [19]WHO 2024. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
  • [20]EMA 2010. https://www.ema.europa.eu/en/documents/press-release/european-medicines-agency-recommends-suspension-marketing-authorisation-sibutramine_en.pdf
  • [21]Klein S, Gastaldelli A, Yki-Järvinen H, Scherer PE. Why does obesity cause diabetes? Cell Metab. 2022; 34(1): 11-20. https://doi.org/10.1016/j.cmet.2021.12.012.
  • [22]Uysal A, Zengin G, Durak Y, Aktumsek A. Screening for antioxidant and antimutagenic properties of extracts from Centaurea pterocaula as well as theirs enzyme inhibitory potentials. Marmara Pharm J. 2016; 20(3): 232-242. https://doi:10.12991/mpj.20162094922.
  • [23]Kocancı FG, Aslım B. Structure and functions of acetylcholinesterase and acetylcholinesterase inhibitory activity of plants. Manas J Agric Vet. 2016; 6(1): 19-35.
  • [24]Uchida R, Ishikawa S, Tomoda H. Inhibition of tyrosinase activity and melanine pigmentation by 2-hydroxytyrosol. Acta Pharm Sin B. 2014; 4(2): 141-145. https://doi.org/10.1016/j.apsb.2013.12.008.
  • [25]Mathus‐Vliegen E, Van Ierland‐Van Leeuwen M, Terpstra A. Lipase inhibition by orlistat: effects on gall‐bladder kinetics and cholecystokinin release in obesity. Aliment Pharmacol. 2004; 19(5): 601-611. https://doi.org/10.1046/j.1365-2036.2004.01812.x.
  • [26]Dal S, Sigrist S. The protective effect of antioxidants consumption on diabetes and vascular complications. Diseases. 2016; 4(3): 24. https://doi.org/10.3390/diseases4030024.
  • [27]García-Fontana B, Morales-Santana S, Longobardo V, Reyes-García R, Rozas-Moreno P, García-Salcedo JA, Muñoz-Torres M. Relationship between proinflammatory and antioxidant proteins with the severity of cardiovascular disease in type 2 diabetes mellitus. Int J Mol Sci. 2015; 16(5): 9469-9483. https://doi.org/10.3390/ijms16059469.
  • [28]Dahlin JL, Inglese J, Walters MA. Mitigating risk in academic preclinical drug discovery. Nat Rev Drug Discov. 2015; 14(4): 279-294. https://doi.org/10.1038/nrd4578. [29]Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol. 2014; 32(1): 40-51. https://doi.org/10.1038/nbt.2786.
  • [30]Sener SO, Ozgen U, Kanbolat S, Korkmaz N, Badem M, Hanci H, Dirmenci T, Arabaci T, Aliyazicioglu R, Yenilmez E. Investigation of therapeutic potential of three endemic Cirsium species for global health problem obesity. S Afr J Bot. 2021; 141: 243-254. https://doi.org/10.1016/j.sajb.2021.05.004.
  • [31]Palanisamy UD, Ling LT, Manaharan T, Appleton D. Rapid isolation of geraniin from Nephelium lappaceum rind waste and its anti-hyperglycemic activity. Food Chem. 2011; 127(1): 21-27. https://doi.org/10.1016/j.foodchem.2010.12.070.
  • [32]Zengin G, Uysal A, Gunes E, Aktumsek A. Survey of phytochemical composition and biological effects of three extracts from a wild plant (Cotoneaster nummularia Fisch. et Mey.): A potential source for functional food ingredients and drug formulations. PloS one. 2014; 9(11): e113527. https://doi.org/10.1371/journal.pone.0113527.
  • [33]Masuda T, Yamashita D, Takeda Y, Yonemori S. Screening for tyrosinase inhibitors among extracts of seashore plants and identification of potent inhibitors from Garcinia subelliptica. Biosci Biotechnol Biochem. 2005; 69(1): 197-201. https://doi.org/10.1271/bbb.69.197.
  • [34]Ellman GL, Courtney KD, Andres Jr V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961; 7(2): 88-95. https://doi.org/10.1016/0006-2952(61)90145-9.
  • [35]Standards NCfCL. Susceptibility Testing of Mycobacteria, Nocardiae, and Other Aerobic Actinomycetes: Approved Standard M24-A. NCCLS Wayne, PA, USA; 2003 [36]Barry AL. Standards NCCLS. Methods for determining bactericidal activity of antimicrobial agents: approved guideline. National Committee for Clinical Laboratory Standards Wayne, PA, 1999.
  • [37]Kirby AJ and Schmidt RJ. The antioxidant activity of Chinese herbs for eczema and of placebo herbs—I. J Ethnopharmacol. 1997; 56(2): 103-108. https://doi.org/10.1016/S0378-8741(97)01510-9.
  • [38]Apak R, Güçlü K, Demirata B, Özyürek M, Çelik SE, Bektaşoğlu B, Berker KI, Özyurt D. Comparative evaluation of various total antioxidant capacity assays applied to phenolic compounds with the CUPRAC assay. Molecules. 2007; 12(7): 1496-1547. https://doi.org/10.3390/12071496.
  • [39]Yayli N, Fandakli S, Korkmaz B, Barut B, Renda G, Erik I. Biological evaluation (antimicrobial, antioxidant, and enzyme inhibitions), total phenolic content and volatile chemical compositions of Caucasalia macrophylla (M. Bieb.) B. Nord.(Asteraceae). J Essent Oil-Bear Plants. 2018; 21(5): 1359-1373. https://doi.org/10.1080/0972060X.2018.1551155.
  • [40]Erik İ, Kılıç G, Öztürk E, Karaoğlu ŞA, Yaylı N. Chemical composition, antimicrobial, and lipase enzyme activity of essential oil and solvent extracts from Serapias orientalis subsp. orientalis. Turk J Chem. 2020; 44(6): 1655-1662. https://doi.org/10.3906/kim-2005-51.
  • [41]Rocha S, Rufino AT, Freitas M, Silva AMS, Carvalho F, Fernandes E. Methodologies for assessing pancreatic lipase catalytic activity: A review. Crit Rev Anal Chem. 2023; 54(8): 3038–3065. https://doi.org/10.1080/10408347.2023.2221731.
  • [42]Prieto-Rodriguez JA, Levuok-Mena KP, Cardozo-Munoz JC, Parra-Amin JE, Lopez-Vallejo F, Cuca-Suarez LE, Patino-Ladino OJ. In vitro and in silico study of the a-glucosidase and lipase inhibitory activities of chemical constituents from Piper cumanense (Piperaceae) and synthetic analogs. Plants. 2022; 11: 2188. https://doi.org/10.3390/plants11172188.
  • [43]Unnisa A, Huwaimel B, Almahmoud S, Abouzied AS, Younes KM, Anupama B, Kola PK, Lakshmi NVKC. Design, in silico study, synthesis and in vitro evaluation of some N5-(1H-pyrazol-3-yl)-3H-benzo [d] imidazole-2, 5- diamine derivatives as potential pancreatic lipase inhibitors for anti-obesity activity. Eur Rev Med Pharmacol Sci. 2022; 26: 7245–7255. https://doi.org/10.26355/eurrev_202210_29917.
  • [44]Hasan A, Khan KM, Sher M, Maharvi GM, Nawaz SA, Choudhary M, Atta-ur-Rahman, Supuran CT Synthesis and inhibitory potential towards acetylcholinesterase, butyrylcholinesterase and lipoxygenase of some variably substituted chalcones. J Enzyme Inhib Med Chem. 2005; 20(1): 41-47. https://doi.org/10.1080/14756360400015231.
  • [45]Delogu GL, Begala M, Matos MJ, Crucitti D, Sogos V, Era B, Fais A. A new class of benzo[b]thiophene-chalcones as cholinesterase inhibitors: Synthesis, biological evaluation, molecular docking and ADME studies. Molecules 2024; 29: 3748. https://doi.org/10.3390/molecules29163748.
  • [46]Şenol H, Ghaffari-Moghaddam M, Alim-Toraman GB, Güller U. Novel chalcone derivatives of ursolic acid as acetylcholinesterase inhibitors: Synthesis, characterization, biological activity, ADME prediction, molecular docking and molecular dynamics studies. J Mol Struct. 2024; 1: 1295. https://doi.org/10.1016/j.molstruc.2023.136804.
  • [47]Jeon K-H, Lee E, Jun K-Y, Eom J-E, Kwak SY, Na Y, Kwon Y. Neuroprotective effect of synthetic chalcone derivatives as competitive dual inhibitors against μ-calpain and cathepsin B through the downregulation of tau phosphorylation and insoluble Aβ peptide formation. Eur J Med Chem. 2016; 121: 433-444. https://doi.org/10.1016/j.ejmech.2016.06.008.
  • [48]Ranjbar S, Akbari A, Edraki N, Khoshneviszadeh M, Hemmatian H, Firuzi O, Khoshneviszadeh M. 6-Methoxy-3,4-dihydronaphthalenone chalcone-like derivatives as potent tyrosinase inhibitors and radical scavengers. Lett Drug Des Discov. 2018; 15(11): 1170-1179. https://doi.org/10.2174/1570180815666180219155027.
  • [49]Kobkeatthawin T, Chantrapromma S, Suwunwong T, Rhyman L, Ramasamı YSC, Ponnaduraı Y. Synthesis, molecular docking and tyrosinase inhibitory activity of the decorated methoxy sulfonamide chalcones: In vitro inhibitory effects and the possible binding mode. Sains Malays. 2021; 50(9): 2603-2614. http://doi.org/10.17576/jsm-2021-5009-09.
  • [50]Martínez-Gutiérrez A, Bertran A, Noya T, Pena-Rodríguez E, Gómez-Escalante S, Pascual S, Luis LS, González MC. New chalcone-derived molecule for the topical regulation of hyperpigmentation and skin aging. Pharmaceutics 2024; 16: 1405. https://doi.org/10.3390/pharmaceutics16111405.
  • [51]Rocha S, Sousa A, Ribeiro D, Correia CM, Silva VL, Santos CM, Silva AM, Araújo AN, Fernandes E, Freitas M. A study towards drug discovery for the management of type 2 diabetes mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives. Food Funct. 2019; 10(9): 5510-5520. https://doi.org/10.1039/C9FO01298B.
  • [52]Saleem F, Khan KM, Chigurupati S, Solangi M, Nemala AR, Mushtaq M, Ul-Haq Z, Taha M, Perveen S. Synthesis of azachalcones, their α-amylase, α-glucosidase inhibitory activities, kinetics, and molecular docking studies. Bioorg Chem. 2021; 106: 104489. https://doi.org/10.1016/j.bioorg.2020.104489.
  • [53]Ali M, Khan M, Zaman K, Wadood A, Iqbal M, Alam A, Shah S, Rehman AU, Yousaf M, Rafique R. Chalcones: as potent α-amylase enzyme inhibitors; synthesis, in vitro, and in silico studies. Med Chem. 2021; 17(8): 903-912. https://doi.org/10.2174/1573406416666200611103039.
  • [54]Rai PV, Ramu R, Akhileshwari P, Prabhu S, Prabhune NM, Deepthi PV, Anjana PT, Ganavi D, Vijesh AM, Goh KW, Ahmed MZ, Kumar V. Novel Benzimidazole-endowed chalcones as α-glucosidase and α-amylase inhibitors: An insight into structural and computational studies . Molecules 2024; 29: 5599. https://doi.org/10.3390/molecules29235599.
  • [55]Kur.un]Aktar BS, Adem ., Tatar]Yilmaz G, Hameed ZAH, Oruc]Emre EE. Investigation of ƒ¿]glucosidase and ƒ¿]amylase inhibitory effects of phenoxy chalcones and molecular modeling studies. J Mol Recognit. 2023; 36(11): e3061. https://doi.org/10.1002/jmr.3061.
  • [56]Kaur C, Kapoor HC Antioxidants in fruits and vegetables.the millenniumfs health. Int J Food Sci Technol. 2001; 36(7): 703-725. https://doi.org/10.1111/j.1365-2621.2001.00513.x.
  • [57]Arslan T, Turko.lu EA, .enturk M, Supuran CT. Synthesis and carbonic anhydrase inhibitory properties of novel chalcone substituted benzenesulfonamides. Int Food Sci. 2016; 26(24): 5867-5870. https://doi.org/10.1016/j.bmcl.2016.11.017.
  • [58]Lee Y-J, Lee J-H, Kim Y-H, Kim J-H, Yu S-Y, Kim D-B, Lee JS, Cho ML, Cho J-H, Kim BK. Assessment of the pectolinarin content and the radical scavenging-linked antiobesity activity of Cirsium setidens Nakai extracts. Food Sci Biotechnol. 2015; 24: 2235-2243. https://doi.org/10.1007/s10068-015-0298-2.
  • [59]Cheng Z-J, Lin C-N, Hwang T-L, Teng C-M. Broussochalcone A, a potent antioxidant and effective suppressor of inducible nitric oxide synthase in lipopolysaccharide-activated macrophages. Biochem Pharmacol. 2001; 61(8): 939-946. https://doi.org/10.1016/S0006-2952(01)00543-3.
  • [60]Aoki N, Muko M, Ohta E, Ohta S. C-geranylated chalcones from the stems of Angelica keiskei with superoxide-scavenging activity. J Nat Prod. 2008; 71(7): 1308-1310. https://doi.org/10.1021/np800187f.
  • [61]Williams LK, Zhang X, Caner S, Tysoe C, Nguyen NT, Wicki J, Williams DE, Coleman J, McNeill JH, Yuen V. The amylase inhibitor montbretin A reveals a new glycosidase inhibition motif. Nat Chem Biol. 2015; 11(9): 691-696. https://doi.org/10.1038/nchembio.1865.
  • [62]Roig-Zamboni V, Cobucci-Ponzano B, Iacono R, Ferrara MC, Germany S, Bourne Y, Parenti G, Moracci M, Sulzenbacher G. Structure of human lysosomal acid ƒ¿-glucosidase.a guide for the treatment of Pompe disease. Nat Commun. 2017; 8(1): 1-10. https://doi.org/10.1038/s41467-017-01263-3.
  • [63]Cheung J, Rudolph MJ, Burshteyn F, Cassidy MS, Gary EN, Love J, Franklin MC, Height JJ. Structures of human acetylcholinesterase in complex with pharmacologically important ligands. J Med Chem. 2012; 55(22): 10282-10286. https://doi.org/10.1021/jm300871x.
  • [64]Meden A, Knez D, Juki. M, Brazzolotto X, Gr.i. M, Pi.lar A, Zahirovi. A, Kos J, Nachon F, Svete J. Tryptophan-derived butyrylcholinesterase inhibitors as promising leads against Alzheimer's disease. Chem Comm. 2019; 55(26): 3765-3768. https://doi.org/10.1039/C9CC01330J.
  • [65]Ismaya WT, Rozeboom HJ, Weijn A, Mes JJ, Fusetti F, Wichers HJ, Dijkstra BW. Crystal structure of Agaricus bisporus mushroom tyrosinase: Identity of the tetramer subunits and interaction with tropolone. Biochemistry. 2011; 50(24): 5477-5486. https://doi.org/10.1021/bi200395t.
  • [66]Hermoso J, Pignol D, Kerfelec B, Crenon I, Chapus C, Fontecilla-Camps JC. Lipase activation by nonionic detergents: The crystal structure of the porcine lipase-colipase-tetraethylene glycol monooctyl ether complex. J Biol Chem. 1996; 271(30): 18007-18016. https://doi.org/10.1074/jbc.271.30.18007.
  • [67]Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017; 7(1): 42717. https://doi.org/10.1038/srep42717.
  • [68]Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 1997; 23(1-3): 3-25. https://doi.org/10.1016/j.addr.2012.09.019.
  • [69]Li W, Xu F, Shuai W, Sun H, Yao H, Ma C, Xu S, Yao H, Zhu Z, Yang D-H. Discovery of novel quinoline.chalcone derivatives as potent antitumor agents with microtubule polymerization inhibitory activity. J Med Chem. 2018; 62(2): 993-1013. https://doi.org/10.1021/acs.jmedchem.8b01755.
  • [70]Aponte JC, Castillo D, Estevez Y, Gonzalez G, Arevalo J, Hammond GB, Sauvain M. In vitro and in vivo anti-Leishmania activity of polysubstituted synthetic chalcones. Bioorg Med Chem Lett. 2010; 20(1): 100-103. https://doi.org/10.1016/j.bmcl.2009.11.033.
  • [71]Mello TF, Bitencourt HR, Pedroso RB, Aristides SM, Lonardoni MV, Silveira TG. Leishmanicidal activity of synthetic chalcones in Leishmania (Viannia) braziliensis. Exp Parasitol. 2014; 136: 27-34. https://doi.org/10.1016/j.exppara.2013.11.003.
  • [72]Garcia AR, Oliveira DM, Jesus JB, Souza AM, Sodero ACR, Vermelho AB, Leal IC, Souza ROM, Miranda LS, Pinheiro AS. Identification of chalcone derivatives as inhibitors of Leishmania infantum arginase and promising antileishmanial agents. Front Chem. 2021; 8: 624678. https://doi.org/10.3389/fchem.2020.624678.
  • [73]Staurengo-Ferrari L, Ruiz-Miyazawa KW, Pinho-Ribeiro FA, Fattori V, Zaninelli TH, Badaro-Garcia S, Borghi SM, Carvalho TT, Alves-Filho JC, Cunha TM. Trans-chalcone attenuates pain and inflammation in experimental acute gout arthritis in mice. Front Pharmacol. 2018; 9: 1123. https://doi.org/10.3389/fphar.2018.01123.
  • [74]Dhiyaaldeen SM, Amin ZA, Darvish PH, Mustafa IF, Jamil MM, Rouhollahi E, Abdulla MA. Protective effects of (1-(4-hydroxy-phenyl)-3-m-tolyl-propenone chalcone in indomethacin-induced gastric erosive damage in rats. BMC Vet Res. 2014; 10: 1-14. https://doi.org/10.1186/s12917-014-0303-7.
  • [75]Cancino K, Castro I, Yauri C, Jullian V, Arévalo J, Sauvain M, Adaui V, Castillo D. Toxicity assessment of synthetic chalcones with antileishmanial potential in BALB/c mice. Rev Peru Med Exp. 2021; 38: 424-433. https://doi.org/10.17843/rpmesp.2021.383.6937.
  • [76]Pires DE, Blundell TL, Ascher DB. pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. J Med Chem. 2015; 58(9): 4066-4072. https://doi.org/10.1021/acs.jmedchem.5b00104.
  • [77]Chemıcals Lo. Globally harmonized system of classification and labelling of chemicals (GHS), 2011.
  • [78]Erik İ, Yaylı N, Coşkunçelebi K, Makbul S, Karaoğlu ŞA. Three new dihydroisocoumarin glycosides with antimicrobial activities from Scorzonera aucheriana. Phytochem Lett. 2021; 43: 45-52. https://doi.org/10.1016/j.phytol.2021.02.010.
  • [79]Woods GL, Brown-Elliott BA, Desmond EP, Hall GS, Heifets L, Pfyffer GE, Ridderhof JC, Wallace RJ, Warren NC, Witebsky FG. Susceptibility testing of mycobacteria, nocardiae, and other aerobic actinomycetes. Approved standard, NCCLS document. 2003; M24-A 23: 18.
  • [80]Çelik G, Kılıç G, Kanbolat Ş, Şener SÖ, Karaköse M, Yaylı N, Karaoğlu ŞA. Biological activity, and volatile and phenolic compounds from five Lamiaceae species. Flavour Fragr J. 2021; 36: 223-232. https://doi.org/10.1002/ffj.3636.
  • [81]Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem. 2009; 30(16): 2785-2791. https://doi.org/10.1002/jcc.21256.
  • [82]Jurrus E, Engel D, Star K, Monson K, Brandi J, Felberg LE, Brookes DH, Wilson L, Chen J, Liles K. Improvements to the APBS biomolecular solvation software suite. Prot Sci. 2018; 27(1): 112-128. https://doi.org/10.1002/pro.3280.
  • [83]Discovery Studio Modeling Environment [database on the Internet], 2020.
  • [84]Banerjee P, Kemmler E, Dunkel M, Preissner R. ProTox 3.0: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2024. https://doi.org/10.1093/nar/gkae303.

Evaluation of synthesized methoxy chalcones for therapeutic potential through in vitro and in silico methods

Year 2025, Volume: 29 Issue: 4, 1693 - 1711, 05.07.2025

Zeynep Erik İshak Erik Can Özgür Yalçın , Sıla Özlem Sener , Şengül Alpay Karaoğlu , Gizem Tatar , Nurettin Yaylı , Rezzan Aliyazıcıoğlu

https://doi.org/10.12991/jrespharm.1734661

Abstract

Chalcones are the precursors of flavonoids and have a wide range of biological activities. A series of methoxy chalcones (1-12) were synthesized using the Claisen-Schmidt method and identified by NMR analyses. Enzyme inhibition, antimicrobial, and antioxidant activities of all compounds were investigated. The enzyme kinetics and ADMET profile of the compounds were evaluated by in silico methods. The highest inhibition activities for lipase, AChE, BChE, tyrosinase, α-amylase, and α-glucosidase were observed at the following IC50 values (μg/mL): 7 (39.83±1.1216), 2 (60.39±1.24), 1 (39.79±1.29), 2 (40.40±1.01), 1 (98.61±3.17), and 2 (55.91±1.78), respectively. Compounds 1 and 4 exhibited the highest antioxidant activity against FRAP and CUPRAC tests, while 1 and 3 were the most effective in the DPPH method. All compounds showed the best activity against gram (-) bacteria. The top docking scores were compound 1 against α-amylase and BChE, 2 against α-glucosidase, AChE, and tyrosinase, and 7 against lipase. All compounds met the drug-likeness criteria using the SwissADME. All compounds have high bioavailability with lower toxicity profiles using SwissADME and pkCSM. According to the AMES test, compounds 3, 6, 9, and 10 were predicted to be mutagenic. ProTox (v.3.0) predicts that all compounds have an oral LD50 value of 2100 mg/kg bw and are classified as GHS Category V, indicating relatively low acute toxicity. Overall, the study results indicate that compounds 1 and 2 show promise for animal studies targeting Alzheimer's disease and diabetes, while 7 appears promising for obesity.

Keywords

Chalcones Molecular docking ADMET Enzyme inhibition Antimicrobial Antioxidant

References

  • [1]Rammohan A, Reddy JS, Sravya G, Rao CN, Zyryanov GV. Chalcone synthesis, properties and medicinal applications: a review. Environ Chem Lett. 2020; 18(2): 433-458. https://doi.org/10.1007/s10311-019-00959-w.
  • [2]Rudrapal M, Khan J, Dukhyil AAB, Alarousy RMII, Attah EI, Sharma T, Khairnar SJ, Bendale AR. (Chalcone scaffolds, bioprecursors of flavonoids: Chemistry, bioactivities, and pharmacokinetics. Molecules. 2021; 26(23): 7177. https://doi.org/10.3390/molecules26237177.
  • [3]Gaonkar SL and Vignesh U. Synthesis and pharmacological properties of chalcones: A review. Res Chem Intermediat. 2017; 43(11): 6043-6077. https://doi.org/10.1007/s11164-017-2977-5.
  • [4]Ouyang Y, Li J, Chen X, Fu X, Sun S, Wu Q. Chalcone derivatives: role in anticancer therapy. Biomolecules. 2021; 11(6): 894. https://doi.org/10.3390/biom11060894.
  • [5]Sahu N, Balbhadra S, Choudhary J, Kohli D. Exploring pharmacological significance of chalcone scaffold: A review. Curr Med Chem. 2012; 19(2): 209-225. https://doi.org/10.2174/092986712803414132.
  • [6]Romagnoli R, Baraldi PG, Carrion MD, Cruz-Lopez O, Cara CL, Balzarini J, Hamel E, Canella A, Fabbri E, Gambari R. Hybrid ƒ¿-bromoacryloylamido chalcones. Design, synthesis and biological evaluation Bioorg Med Chem Lett. 2009; 19(7): 2022-2028. https://doi.org/10.1016/j.bmcl.2009.02.038.
  • [7]Sharma A, Chakravarti B, Gupt MP, Siddiqui JA, Konwar R, Tripathi RP. Synthesis and anti breast cancer activity of biphenyl based chalcones. Bioorg Med Chem. 2010; 18(13): 4711-4720. https://doi.org/10.1016/j.bmc.2010.05.015.
  • [8]Saunders KH, Umashanker D, Igel LI, Kumar RB, Aronne LJ. Obesity pharmacotherapy. Med Clin. 2018; 102(1): 135-148. https://doi.org/10.1016/j.mcna.2017.08.010.
  • [9]Akter N, Qureshi NK, Ferdous HS. Obesity: a review of pathogenesis and management strategies in adult. Delta Med Coll J. 2017; 5(1): 35-48. https://doi.org/10.3329/dmcj.v5i1.31436.
  • [10]Watanabe H, Saji H, Ono M. Novel fluorescence probes based on the chalcone scaffold for in vitro staining of ƒÀ-amyloid plaques. Bioorg Med Chem Lett. 2018; 28(19): 3242-3246. https://doi.org/10.1016/j.bmcl.2018.08.009.
  • [11]Nagai H, He JX, Tani T, Akao T. Antispasmodic activity of licochalcone A, a species]specific ingredient of Glycyrrhiza inflata roots. J Pharm Pharmacol. 2007; 59(10): 1421-1426. https://doi.org/10.1211/jpp.59.10.0013.
  • [12]Nazarian Z, Emami S, Heydari S, Ardestani SK, Nakhjiri M, Poorrajab F, Shafiee A, Foroumadi A. Novel antileishmanial chalconoids: Synthesis and biological activity of 1-or 3-(6-chloro-2H-chromen-3-yl) propen-1-ones. Eur J Med Chem. 2010; 45(4): 1424-1429. https://doi.org/10.1016/j.ejmech.2009.12.046
  • [13]Mahapatra DK, Asati V, Bharti SK. Chalcones and their therapeutic targets for the management of diabetes: structural and pharmacological perspectives. Eur J Med Chem. 2015; 92: 839-865. https://doi.org/10.1016/j.ejmech.2015.01.051.
  • [14]Damazio RG, Zanatta AP, Cazarolli LH, Chiaradia LD, Mascarello A, Nunes RJ, Yunes RA, Silva FRMB. Antihyperglycemic activity of naphthylchalcones. Eur J Med Chem. 2010; 45(4): 1332-1337. https://doi.org/10.1016/j.ejmech.2009.12.017.
  • [15]Sashidhara KV, Kumar M, Modukuri RK, Sonkar R, Bhatia G, Khanna A, Rai S, Shukla R. Synthesis and anti-inflammatory activity of novel biscoumarin–chalcone hybrids. Bioorg Med Chem Lett. 2011; 21(15): 4480-4484. https://doi.org/10.1016/j.bmcl.2011.06.002.
  • [16]Singh AK, Singh R. Pharmacotherapy in obesity: A systematic review and meta-analysis of randomized controlled trials of anti-obesity drugs. Expert Rev Clin Pharmacol. 2020; 13(1): 53-64. https://doi.org/10.1080/17512433.2020.1698291.
  • [17]Berhane HY, Jirström M, Abdelmenan S, Berhane Y, Alsanius B, Trenholm J, Ekström E-C. Social stratification, diet diversity and malnutrition among preschoolers: a survey of Addis Ababa, Ethiopia. Nutrients. 2020; 12(3): 712. https://doi.org/10.3390/nu12030712.
  • [18]Toader C, Tataru CP, Munteanu O, Serban M, Covache-Busuioc RA, Ciurea AV, Enyedi M. Decoding Neurodegeneration: A review of molecular mechanisms and therapeutic advances in Alzheimer's, Parkinson's, and ALS. Int J Mol Sci. 2024; 25(23): 12613. https://doi.org/10.3390/ijms252312613.
  • [19]WHO 2024. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
  • [20]EMA 2010. https://www.ema.europa.eu/en/documents/press-release/european-medicines-agency-recommends-suspension-marketing-authorisation-sibutramine_en.pdf
  • [21]Klein S, Gastaldelli A, Yki-Järvinen H, Scherer PE. Why does obesity cause diabetes? Cell Metab. 2022; 34(1): 11-20. https://doi.org/10.1016/j.cmet.2021.12.012.
  • [22]Uysal A, Zengin G, Durak Y, Aktumsek A. Screening for antioxidant and antimutagenic properties of extracts from Centaurea pterocaula as well as theirs enzyme inhibitory potentials. Marmara Pharm J. 2016; 20(3): 232-242. https://doi:10.12991/mpj.20162094922.
  • [23]Kocancı FG, Aslım B. Structure and functions of acetylcholinesterase and acetylcholinesterase inhibitory activity of plants. Manas J Agric Vet. 2016; 6(1): 19-35.
  • [24]Uchida R, Ishikawa S, Tomoda H. Inhibition of tyrosinase activity and melanine pigmentation by 2-hydroxytyrosol. Acta Pharm Sin B. 2014; 4(2): 141-145. https://doi.org/10.1016/j.apsb.2013.12.008.
  • [25]Mathus‐Vliegen E, Van Ierland‐Van Leeuwen M, Terpstra A. Lipase inhibition by orlistat: effects on gall‐bladder kinetics and cholecystokinin release in obesity. Aliment Pharmacol. 2004; 19(5): 601-611. https://doi.org/10.1046/j.1365-2036.2004.01812.x.
  • [26]Dal S, Sigrist S. The protective effect of antioxidants consumption on diabetes and vascular complications. Diseases. 2016; 4(3): 24. https://doi.org/10.3390/diseases4030024.
  • [27]García-Fontana B, Morales-Santana S, Longobardo V, Reyes-García R, Rozas-Moreno P, García-Salcedo JA, Muñoz-Torres M. Relationship between proinflammatory and antioxidant proteins with the severity of cardiovascular disease in type 2 diabetes mellitus. Int J Mol Sci. 2015; 16(5): 9469-9483. https://doi.org/10.3390/ijms16059469.
  • [28]Dahlin JL, Inglese J, Walters MA. Mitigating risk in academic preclinical drug discovery. Nat Rev Drug Discov. 2015; 14(4): 279-294. https://doi.org/10.1038/nrd4578. [29]Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol. 2014; 32(1): 40-51. https://doi.org/10.1038/nbt.2786.
  • [30]Sener SO, Ozgen U, Kanbolat S, Korkmaz N, Badem M, Hanci H, Dirmenci T, Arabaci T, Aliyazicioglu R, Yenilmez E. Investigation of therapeutic potential of three endemic Cirsium species for global health problem obesity. S Afr J Bot. 2021; 141: 243-254. https://doi.org/10.1016/j.sajb.2021.05.004.
  • [31]Palanisamy UD, Ling LT, Manaharan T, Appleton D. Rapid isolation of geraniin from Nephelium lappaceum rind waste and its anti-hyperglycemic activity. Food Chem. 2011; 127(1): 21-27. https://doi.org/10.1016/j.foodchem.2010.12.070.
  • [32]Zengin G, Uysal A, Gunes E, Aktumsek A. Survey of phytochemical composition and biological effects of three extracts from a wild plant (Cotoneaster nummularia Fisch. et Mey.): A potential source for functional food ingredients and drug formulations. PloS one. 2014; 9(11): e113527. https://doi.org/10.1371/journal.pone.0113527.
  • [33]Masuda T, Yamashita D, Takeda Y, Yonemori S. Screening for tyrosinase inhibitors among extracts of seashore plants and identification of potent inhibitors from Garcinia subelliptica. Biosci Biotechnol Biochem. 2005; 69(1): 197-201. https://doi.org/10.1271/bbb.69.197.
  • [34]Ellman GL, Courtney KD, Andres Jr V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961; 7(2): 88-95. https://doi.org/10.1016/0006-2952(61)90145-9.
  • [35]Standards NCfCL. Susceptibility Testing of Mycobacteria, Nocardiae, and Other Aerobic Actinomycetes: Approved Standard M24-A. NCCLS Wayne, PA, USA; 2003 [36]Barry AL. Standards NCCLS. Methods for determining bactericidal activity of antimicrobial agents: approved guideline. National Committee for Clinical Laboratory Standards Wayne, PA, 1999.
  • [37]Kirby AJ and Schmidt RJ. The antioxidant activity of Chinese herbs for eczema and of placebo herbs—I. J Ethnopharmacol. 1997; 56(2): 103-108. https://doi.org/10.1016/S0378-8741(97)01510-9.
  • [38]Apak R, Güçlü K, Demirata B, Özyürek M, Çelik SE, Bektaşoğlu B, Berker KI, Özyurt D. Comparative evaluation of various total antioxidant capacity assays applied to phenolic compounds with the CUPRAC assay. Molecules. 2007; 12(7): 1496-1547. https://doi.org/10.3390/12071496.
  • [39]Yayli N, Fandakli S, Korkmaz B, Barut B, Renda G, Erik I. Biological evaluation (antimicrobial, antioxidant, and enzyme inhibitions), total phenolic content and volatile chemical compositions of Caucasalia macrophylla (M. Bieb.) B. Nord.(Asteraceae). J Essent Oil-Bear Plants. 2018; 21(5): 1359-1373. https://doi.org/10.1080/0972060X.2018.1551155.
  • [40]Erik İ, Kılıç G, Öztürk E, Karaoğlu ŞA, Yaylı N. Chemical composition, antimicrobial, and lipase enzyme activity of essential oil and solvent extracts from Serapias orientalis subsp. orientalis. Turk J Chem. 2020; 44(6): 1655-1662. https://doi.org/10.3906/kim-2005-51.
  • [41]Rocha S, Rufino AT, Freitas M, Silva AMS, Carvalho F, Fernandes E. Methodologies for assessing pancreatic lipase catalytic activity: A review. Crit Rev Anal Chem. 2023; 54(8): 3038–3065. https://doi.org/10.1080/10408347.2023.2221731.
  • [42]Prieto-Rodriguez JA, Levuok-Mena KP, Cardozo-Munoz JC, Parra-Amin JE, Lopez-Vallejo F, Cuca-Suarez LE, Patino-Ladino OJ. In vitro and in silico study of the a-glucosidase and lipase inhibitory activities of chemical constituents from Piper cumanense (Piperaceae) and synthetic analogs. Plants. 2022; 11: 2188. https://doi.org/10.3390/plants11172188.
  • [43]Unnisa A, Huwaimel B, Almahmoud S, Abouzied AS, Younes KM, Anupama B, Kola PK, Lakshmi NVKC. Design, in silico study, synthesis and in vitro evaluation of some N5-(1H-pyrazol-3-yl)-3H-benzo [d] imidazole-2, 5- diamine derivatives as potential pancreatic lipase inhibitors for anti-obesity activity. Eur Rev Med Pharmacol Sci. 2022; 26: 7245–7255. https://doi.org/10.26355/eurrev_202210_29917.
  • [44]Hasan A, Khan KM, Sher M, Maharvi GM, Nawaz SA, Choudhary M, Atta-ur-Rahman, Supuran CT Synthesis and inhibitory potential towards acetylcholinesterase, butyrylcholinesterase and lipoxygenase of some variably substituted chalcones. J Enzyme Inhib Med Chem. 2005; 20(1): 41-47. https://doi.org/10.1080/14756360400015231.
  • [45]Delogu GL, Begala M, Matos MJ, Crucitti D, Sogos V, Era B, Fais A. A new class of benzo[b]thiophene-chalcones as cholinesterase inhibitors: Synthesis, biological evaluation, molecular docking and ADME studies. Molecules 2024; 29: 3748. https://doi.org/10.3390/molecules29163748.
  • [46]Şenol H, Ghaffari-Moghaddam M, Alim-Toraman GB, Güller U. Novel chalcone derivatives of ursolic acid as acetylcholinesterase inhibitors: Synthesis, characterization, biological activity, ADME prediction, molecular docking and molecular dynamics studies. J Mol Struct. 2024; 1: 1295. https://doi.org/10.1016/j.molstruc.2023.136804.
  • [47]Jeon K-H, Lee E, Jun K-Y, Eom J-E, Kwak SY, Na Y, Kwon Y. Neuroprotective effect of synthetic chalcone derivatives as competitive dual inhibitors against μ-calpain and cathepsin B through the downregulation of tau phosphorylation and insoluble Aβ peptide formation. Eur J Med Chem. 2016; 121: 433-444. https://doi.org/10.1016/j.ejmech.2016.06.008.
  • [48]Ranjbar S, Akbari A, Edraki N, Khoshneviszadeh M, Hemmatian H, Firuzi O, Khoshneviszadeh M. 6-Methoxy-3,4-dihydronaphthalenone chalcone-like derivatives as potent tyrosinase inhibitors and radical scavengers. Lett Drug Des Discov. 2018; 15(11): 1170-1179. https://doi.org/10.2174/1570180815666180219155027.
  • [49]Kobkeatthawin T, Chantrapromma S, Suwunwong T, Rhyman L, Ramasamı YSC, Ponnaduraı Y. Synthesis, molecular docking and tyrosinase inhibitory activity of the decorated methoxy sulfonamide chalcones: In vitro inhibitory effects and the possible binding mode. Sains Malays. 2021; 50(9): 2603-2614. http://doi.org/10.17576/jsm-2021-5009-09.
  • [50]Martínez-Gutiérrez A, Bertran A, Noya T, Pena-Rodríguez E, Gómez-Escalante S, Pascual S, Luis LS, González MC. New chalcone-derived molecule for the topical regulation of hyperpigmentation and skin aging. Pharmaceutics 2024; 16: 1405. https://doi.org/10.3390/pharmaceutics16111405.
  • [51]Rocha S, Sousa A, Ribeiro D, Correia CM, Silva VL, Santos CM, Silva AM, Araújo AN, Fernandes E, Freitas M. A study towards drug discovery for the management of type 2 diabetes mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives. Food Funct. 2019; 10(9): 5510-5520. https://doi.org/10.1039/C9FO01298B.
  • [52]Saleem F, Khan KM, Chigurupati S, Solangi M, Nemala AR, Mushtaq M, Ul-Haq Z, Taha M, Perveen S. Synthesis of azachalcones, their α-amylase, α-glucosidase inhibitory activities, kinetics, and molecular docking studies. Bioorg Chem. 2021; 106: 104489. https://doi.org/10.1016/j.bioorg.2020.104489.
  • [53]Ali M, Khan M, Zaman K, Wadood A, Iqbal M, Alam A, Shah S, Rehman AU, Yousaf M, Rafique R. Chalcones: as potent α-amylase enzyme inhibitors; synthesis, in vitro, and in silico studies. Med Chem. 2021; 17(8): 903-912. https://doi.org/10.2174/1573406416666200611103039.
  • [54]Rai PV, Ramu R, Akhileshwari P, Prabhu S, Prabhune NM, Deepthi PV, Anjana PT, Ganavi D, Vijesh AM, Goh KW, Ahmed MZ, Kumar V. Novel Benzimidazole-endowed chalcones as α-glucosidase and α-amylase inhibitors: An insight into structural and computational studies . Molecules 2024; 29: 5599. https://doi.org/10.3390/molecules29235599.
  • [55]Kur.un]Aktar BS, Adem ., Tatar]Yilmaz G, Hameed ZAH, Oruc]Emre EE. Investigation of ƒ¿]glucosidase and ƒ¿]amylase inhibitory effects of phenoxy chalcones and molecular modeling studies. J Mol Recognit. 2023; 36(11): e3061. https://doi.org/10.1002/jmr.3061.
  • [56]Kaur C, Kapoor HC Antioxidants in fruits and vegetables.the millenniumfs health. Int J Food Sci Technol. 2001; 36(7): 703-725. https://doi.org/10.1111/j.1365-2621.2001.00513.x.
  • [57]Arslan T, Turko.lu EA, .enturk M, Supuran CT. Synthesis and carbonic anhydrase inhibitory properties of novel chalcone substituted benzenesulfonamides. Int Food Sci. 2016; 26(24): 5867-5870. https://doi.org/10.1016/j.bmcl.2016.11.017.
  • [58]Lee Y-J, Lee J-H, Kim Y-H, Kim J-H, Yu S-Y, Kim D-B, Lee JS, Cho ML, Cho J-H, Kim BK. Assessment of the pectolinarin content and the radical scavenging-linked antiobesity activity of Cirsium setidens Nakai extracts. Food Sci Biotechnol. 2015; 24: 2235-2243. https://doi.org/10.1007/s10068-015-0298-2.
  • [59]Cheng Z-J, Lin C-N, Hwang T-L, Teng C-M. Broussochalcone A, a potent antioxidant and effective suppressor of inducible nitric oxide synthase in lipopolysaccharide-activated macrophages. Biochem Pharmacol. 2001; 61(8): 939-946. https://doi.org/10.1016/S0006-2952(01)00543-3.
  • [60]Aoki N, Muko M, Ohta E, Ohta S. C-geranylated chalcones from the stems of Angelica keiskei with superoxide-scavenging activity. J Nat Prod. 2008; 71(7): 1308-1310. https://doi.org/10.1021/np800187f.
  • [61]Williams LK, Zhang X, Caner S, Tysoe C, Nguyen NT, Wicki J, Williams DE, Coleman J, McNeill JH, Yuen V. The amylase inhibitor montbretin A reveals a new glycosidase inhibition motif. Nat Chem Biol. 2015; 11(9): 691-696. https://doi.org/10.1038/nchembio.1865.
  • [62]Roig-Zamboni V, Cobucci-Ponzano B, Iacono R, Ferrara MC, Germany S, Bourne Y, Parenti G, Moracci M, Sulzenbacher G. Structure of human lysosomal acid ƒ¿-glucosidase.a guide for the treatment of Pompe disease. Nat Commun. 2017; 8(1): 1-10. https://doi.org/10.1038/s41467-017-01263-3.
  • [63]Cheung J, Rudolph MJ, Burshteyn F, Cassidy MS, Gary EN, Love J, Franklin MC, Height JJ. Structures of human acetylcholinesterase in complex with pharmacologically important ligands. J Med Chem. 2012; 55(22): 10282-10286. https://doi.org/10.1021/jm300871x.
  • [64]Meden A, Knez D, Juki. M, Brazzolotto X, Gr.i. M, Pi.lar A, Zahirovi. A, Kos J, Nachon F, Svete J. Tryptophan-derived butyrylcholinesterase inhibitors as promising leads against Alzheimer's disease. Chem Comm. 2019; 55(26): 3765-3768. https://doi.org/10.1039/C9CC01330J.
  • [65]Ismaya WT, Rozeboom HJ, Weijn A, Mes JJ, Fusetti F, Wichers HJ, Dijkstra BW. Crystal structure of Agaricus bisporus mushroom tyrosinase: Identity of the tetramer subunits and interaction with tropolone. Biochemistry. 2011; 50(24): 5477-5486. https://doi.org/10.1021/bi200395t.
  • [66]Hermoso J, Pignol D, Kerfelec B, Crenon I, Chapus C, Fontecilla-Camps JC. Lipase activation by nonionic detergents: The crystal structure of the porcine lipase-colipase-tetraethylene glycol monooctyl ether complex. J Biol Chem. 1996; 271(30): 18007-18016. https://doi.org/10.1074/jbc.271.30.18007.
  • [67]Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017; 7(1): 42717. https://doi.org/10.1038/srep42717.
  • [68]Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 1997; 23(1-3): 3-25. https://doi.org/10.1016/j.addr.2012.09.019.
  • [69]Li W, Xu F, Shuai W, Sun H, Yao H, Ma C, Xu S, Yao H, Zhu Z, Yang D-H. Discovery of novel quinoline.chalcone derivatives as potent antitumor agents with microtubule polymerization inhibitory activity. J Med Chem. 2018; 62(2): 993-1013. https://doi.org/10.1021/acs.jmedchem.8b01755.
  • [70]Aponte JC, Castillo D, Estevez Y, Gonzalez G, Arevalo J, Hammond GB, Sauvain M. In vitro and in vivo anti-Leishmania activity of polysubstituted synthetic chalcones. Bioorg Med Chem Lett. 2010; 20(1): 100-103. https://doi.org/10.1016/j.bmcl.2009.11.033.
  • [71]Mello TF, Bitencourt HR, Pedroso RB, Aristides SM, Lonardoni MV, Silveira TG. Leishmanicidal activity of synthetic chalcones in Leishmania (Viannia) braziliensis. Exp Parasitol. 2014; 136: 27-34. https://doi.org/10.1016/j.exppara.2013.11.003.
  • [72]Garcia AR, Oliveira DM, Jesus JB, Souza AM, Sodero ACR, Vermelho AB, Leal IC, Souza ROM, Miranda LS, Pinheiro AS. Identification of chalcone derivatives as inhibitors of Leishmania infantum arginase and promising antileishmanial agents. Front Chem. 2021; 8: 624678. https://doi.org/10.3389/fchem.2020.624678.
  • [73]Staurengo-Ferrari L, Ruiz-Miyazawa KW, Pinho-Ribeiro FA, Fattori V, Zaninelli TH, Badaro-Garcia S, Borghi SM, Carvalho TT, Alves-Filho JC, Cunha TM. Trans-chalcone attenuates pain and inflammation in experimental acute gout arthritis in mice. Front Pharmacol. 2018; 9: 1123. https://doi.org/10.3389/fphar.2018.01123.
  • [74]Dhiyaaldeen SM, Amin ZA, Darvish PH, Mustafa IF, Jamil MM, Rouhollahi E, Abdulla MA. Protective effects of (1-(4-hydroxy-phenyl)-3-m-tolyl-propenone chalcone in indomethacin-induced gastric erosive damage in rats. BMC Vet Res. 2014; 10: 1-14. https://doi.org/10.1186/s12917-014-0303-7.
  • [75]Cancino K, Castro I, Yauri C, Jullian V, Arévalo J, Sauvain M, Adaui V, Castillo D. Toxicity assessment of synthetic chalcones with antileishmanial potential in BALB/c mice. Rev Peru Med Exp. 2021; 38: 424-433. https://doi.org/10.17843/rpmesp.2021.383.6937.
  • [76]Pires DE, Blundell TL, Ascher DB. pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. J Med Chem. 2015; 58(9): 4066-4072. https://doi.org/10.1021/acs.jmedchem.5b00104.
  • [77]Chemıcals Lo. Globally harmonized system of classification and labelling of chemicals (GHS), 2011.
  • [78]Erik İ, Yaylı N, Coşkunçelebi K, Makbul S, Karaoğlu ŞA. Three new dihydroisocoumarin glycosides with antimicrobial activities from Scorzonera aucheriana. Phytochem Lett. 2021; 43: 45-52. https://doi.org/10.1016/j.phytol.2021.02.010.
  • [79]Woods GL, Brown-Elliott BA, Desmond EP, Hall GS, Heifets L, Pfyffer GE, Ridderhof JC, Wallace RJ, Warren NC, Witebsky FG. Susceptibility testing of mycobacteria, nocardiae, and other aerobic actinomycetes. Approved standard, NCCLS document. 2003; M24-A 23: 18.
  • [80]Çelik G, Kılıç G, Kanbolat Ş, Şener SÖ, Karaköse M, Yaylı N, Karaoğlu ŞA. Biological activity, and volatile and phenolic compounds from five Lamiaceae species. Flavour Fragr J. 2021; 36: 223-232. https://doi.org/10.1002/ffj.3636.
  • [81]Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem. 2009; 30(16): 2785-2791. https://doi.org/10.1002/jcc.21256.
  • [82]Jurrus E, Engel D, Star K, Monson K, Brandi J, Felberg LE, Brookes DH, Wilson L, Chen J, Liles K. Improvements to the APBS biomolecular solvation software suite. Prot Sci. 2018; 27(1): 112-128. https://doi.org/10.1002/pro.3280.
  • [83]Discovery Studio Modeling Environment [database on the Internet], 2020.
  • [84]Banerjee P, Kemmler E, Dunkel M, Preissner R. ProTox 3.0: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2024. https://doi.org/10.1093/nar/gkae303.
There are 82 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences (Other)
Journal Section Articles
Authors

Zeynep Erik

İshak Erik

Can Özgür Yalçın

Sıla Özlem Sener

Şengül Alpay Karaoğlu

Gizem Tatar

Nurettin Yaylı

Rezzan Aliyazıcıoğlu

Publication Date July 5, 2025
Submission Date October 24, 2024
Acceptance Date January 31, 2025
Published in Issue Year 2025 Volume: 29 Issue: 4

Cite

APA Erik, Z., Erik, İ., Yalçın, C. Ö., Sener, S. Ö., et al. (2025). Evaluation of synthesized methoxy chalcones for therapeutic potential through in vitro and in silico methods. Journal of Research in Pharmacy, 29(4), 1693-1711. https://doi.org/10.12991/jrespharm.1734661
AMA Erik Z, Erik İ, Yalçın CÖ, Sener SÖ, Alpay Karaoğlu Ş, Tatar G, Yaylı N, Aliyazıcıoğlu R. Evaluation of synthesized methoxy chalcones for therapeutic potential through in vitro and in silico methods. J. Res. Pharm. July 2025;29(4):1693-1711. doi:10.12991/jrespharm.1734661
Chicago Erik, Zeynep, İshak Erik, Can Özgür Yalçın, Sıla Özlem Sener, Şengül Alpay Karaoğlu, Gizem Tatar, Nurettin Yaylı, and Rezzan Aliyazıcıoğlu. “Evaluation of Synthesized Methoxy Chalcones for Therapeutic Potential through in Vitro and in Silico Methods”. Journal of Research in Pharmacy 29, no. 4 (July 2025): 1693-1711. https://doi.org/10.12991/jrespharm.1734661.
EndNote Erik Z, Erik İ, Yalçın CÖ, Sener SÖ, Alpay Karaoğlu Ş, Tatar G, Yaylı N, Aliyazıcıoğlu R (July 1, 2025) Evaluation of synthesized methoxy chalcones for therapeutic potential through in vitro and in silico methods. Journal of Research in Pharmacy 29 4 1693–1711.
IEEE Z. Erik, İ. Erik, C. Ö. Yalçın, S. Ö. Sener, Ş. Alpay Karaoğlu, G. Tatar, N. Yaylı, and R. Aliyazıcıoğlu, “Evaluation of synthesized methoxy chalcones for therapeutic potential through in vitro and in silico methods”, J. Res. Pharm., vol. 29, no. 4, pp. 1693–1711, 2025, doi: 10.12991/jrespharm.1734661.
ISNAD Erik, Zeynep et al. “Evaluation of Synthesized Methoxy Chalcones for Therapeutic Potential through in Vitro and in Silico Methods”. Journal of Research in Pharmacy 29/4 (July 2025), 1693-1711. https://doi.org/10.12991/jrespharm.1734661.
JAMA Erik Z, Erik İ, Yalçın CÖ, Sener SÖ, Alpay Karaoğlu Ş, Tatar G, Yaylı N, Aliyazıcıoğlu R. Evaluation of synthesized methoxy chalcones for therapeutic potential through in vitro and in silico methods. J. Res. Pharm. 2025;29:1693–1711.
MLA Erik, Zeynep et al. “Evaluation of Synthesized Methoxy Chalcones for Therapeutic Potential through in Vitro and in Silico Methods”. Journal of Research in Pharmacy, vol. 29, no. 4, 2025, pp. 1693-11, doi:10.12991/jrespharm.1734661.
Vancouver Erik Z, Erik İ, Yalçın CÖ, Sener SÖ, Alpay Karaoğlu Ş, Tatar G, Yaylı N, Aliyazıcıoğlu R. Evaluation of synthesized methoxy chalcones for therapeutic potential through in vitro and in silico methods. J. Res. Pharm. 2025;29(4):1693-711.