Araştırma Makalesi
BibTex RIS Kaynak Göster

In silico investigation of novel 5-benzylidene-2- (arylsulfonylhydrazono)thiazolidine-4-ones as potential inhibitors of mPGES-1 and COX-2

Yıl 2023, Cilt: 27 Sayı: 5, 2124 - 2134, 28.06.2025

Necla Kulabaş

Öz

Studies on the development of safe anti-inflammatory agents targeting the inhibition of the mPGES-1 enzyme responsible for PGE2 production are increasing day by day. Moreover, selective inhibition of the mPGES-1 enzyme which modulates the tumor microenvironment and inhibits tumor growth, making the mPGES-1 enzyme one of the important macromolecular targets in cancer therapy. The aim of our study was to develop selective mPGES-1 inhibitors and to determine their in silico mPGES-1 enzyme inhibition potential. In this study, the binding affinities of 14 novel designed 5-benzylidene-2-(arylsulfonylhydrazono)thiazolidine-4-one derivatives were investigated against mPGES-1 and COX-2 enzymes by computer-aided molecular modeling studies. Among the designed compounds 1-14, it was presented with in silico data that compound 8-14, which does not interact with the active site of the COX-2 enzyme, exhibited selective binding with mPGES-1 enzyme. Moreover, compounds 10-13 have been suggested as selective mPGES-1 inhibitors with a better in silico binding energy than the first discovered mPGES-1 inhibitor MK886. Finally, ADMET profiles of compounds 1-14 were calculated. None of these compounds violated the Lipinski and Veber rules.

Anahtar Kelimeler

4-Thiazolidinone mPGES-1 COX-2 in silico ADMET

Kaynakça

  • [1] Al-Turki DA, Abou-Zeid LA, Shehata LA, Al-Omar MA. Therapeutic and Toxic Effects of New NSAIDs and Related Compounds: A Review and Prospective Study. Int J Pharmacol. 2010; 6: 813–825.
  • [2] Hassan GS, Abou-Seri SM, Kamel G, Ali MM. Celecoxib analogs bearing benzofuran moiety as cyclooxygenase-2 inhibitors: Design, synthesis and evaluation as potential anti-inflammatory agents. Eur J Med Chem. 2014; 76: 482–493. https://doi.org/10.1016/j.ejmech.2014.02.033
  • [3] Basile L, Alvarez S, Blanco A, Santagati A, Granata G, Di Pietro P, Guccione S, Muñoz-Fernández MÁ. Sulfonilamidothiopyrimidone and thiopyrimidone derivatives as selective COX-2 inhibitors: synthesis, biological evaluation, and docking studies. Eur J Med Chem. 2012; 57: 149–161. https://doi.org/10.1016/j.ejmech.2012.09.005
  • [4] Chen WC, Tseng CK, Chen YH, Lin CK, Hsu S, Wang SN, Lee JC. HCV NS5A up-regulates COX-2 expression via IL-8-mediated activation of the ERK/JNK MAPK pathway. PLoS One. 2015; 10: 1–21. https://doi.org/10.1371/journal.pone.0133264
  • [5] Sjögren T, Nord J, Ek M, Johansson P, Liu G, Geschwindner S. Crystal structure of microsomal prostaglandin E2 synthase provides insight into diversity in the MAPEG superfamily. Proc Natl Acad Sci U S A. 2013; 110: 3806–3811. https://doi.org/10.1073/pnas.1218504110
  • [6] Akasaka H, So SP, Ruan KH. Relationship of the Topological Distances and Activities between mPGES-1 and COX-2 versus COX-1: Implications of the Different Post-Translational Endoplasmic Reticulum Organizations of COX-1 and COX-2. Biochemistry. 2015; 54: 3707–3715. https://doi.org/10.1021/acs.biochem.5b00339
  • [7] Perry LA, Mosler C, Atkins A, Minehart M. Cardiovascular Risk Associated With NSAIDs and COX-2 Inhibitors. US Pharm. 2014; 39: 35–38.
  • [8] Muthukaman N, Deshmukh S, Tambe M, Pisal D, Tondlekar S, Shaikh M, et al. Alleviating CYP and hERG liabilities by structure optimization of dihydrofuran-fused tricyclic benzo[d]imidazole series – Potent, selective and orally efficacious microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors: Part-2. Bioorg Med Chem Lett. 2018; 28: 1211–1218. https://doi.org/10.1016/j.bmcl.2018.02.048
  • [9] Ding K, Zhou Z, Zhou S, Yuan Y, Kim K, Zhang T, Zheng X, Zheng F, Zhan CG. Design, synthesis, and discovery of 5-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-triones and related derivatives as novel inhibitors of mPGES-1. Bioorg Med Chem Lett. 2018; 28: 858–862. https://doi.org/10.1016/j.bmcl.2018.02.011
  • [10] Ding K, Zhou Z, Hou S, Yuan Y, Zhou S, Zheng X, Chen J, Loftin C, Zheng F, Zhan C-G. Structure-based discovery of mPGES-1 inhibitors suitable for preclinical testing in wild-type mice as a new generation of anti-inflammatory drugs. Sci Rep. 2018; 8: 5205. https://doi.org/10.1038/s41598-018-23482-4
  • [11] Koeberle A, Werz O. Perspective of microsomal prostaglandin E2 synthase-1 as drug target in inflammation-related disorders. Biochem Pharmacol. 2015; 98: 1–15. https://doi.org/10.1016/j.bcp.2015.06.022
  • [12] Koeberle A, Laufer SA, Werz O. Design and Development of Microsomal Prostaglandin E2 Synthase-1 Inhibitors: Challenges and Future Directions. J Med Chem. 2016; 59: 5970–5986. https://doi.org/10.1021/acs.jmedchem.5b01750
  • [13] Mancini JA, Blood K, Guay J, Gordon R, Claveau D, Chan CC, Riendeau D. Cloning, Expression, and Up-regulation of Inducible Rat Prostaglandin E Synthase during Lipopolysaccharide-induced Pyresis and Adjuvant-induced Arthritis. J Biol Chem. 2001; 276: 4469–4475. https://doi.org/10.1074/jbc.M006865200
  • [14] Xu D, Rowland SE, Clark P, Giroux A, Côté B, Guiral S, et al. MF63 [2-(6-chloro-1H-phenanthro[9,10-d]imidazol-2-yl)-isophthalonitrile], a selective microsomal prostaglandin E synthase-1 inhibitor, relieves pyresis and pain in preclinical models of inflammation. J Pharmacol Exp Ther. 2008; 326: 754–763. https://doi.org/10.1124/jpet.108.138776
  • [15] Arhancet GB, Walker DP, Metz S, Fobian YM, Heasley SE, Carter JS, et al. Discovery and SAR of PF-4693627, a potent, selective and orally bioavailable mPGES-1 inhibitor for the potential treatment of inflammation. Bioorg Med Chem Lett. 2013; 23: 1114–1119. https://doi.org/10.1016/j.bmcl.2012.11.109
  • [16] Banerjee A, Pawar MY, Patil S, Yadav PS, Kadam PA, Kattige VG, et al. Development of 2-aryl substituted quinazolin-4(3H)-one, pyrido[4,3-d]pyrimidin-4(3H)-one and pyrido[2,3-d]pyrimidin-4(3H)-one derivatives as microsomal prostaglandin E2 synthase-1 inhibitors. Bioorg Med Chem Lett. 2014; 24: 4838–4844. https://doi.org/10.1016/j.bmcl.2014.08.056
  • [17] Schiffler MA, Antonysamy S, Bhattachar SN, Campanale KM, Chandrasekhar S, Condon B, et al. Discovery and Characterization of 2-Acylaminoimidazole Microsomal Prostaglandin E Synthase-1 Inhibitors. J Med Chem. 2016; 59: 194–205. https://doi.org/10.1021/acs.jmedchem.5b01249
  • [18] Wannberg J. Piperidinyl benzoimidazole derivatives as mPGES-1 inhibitors. US Patent 2016/0122330 A1, 2016.
  • [19] Priepke H, Doods H, Kuelzer R, Pfau R. 3H-imidazo[4,5-C]pyridine-6-carboxamides as anti-inflammatory agents. US Patent US8759537B2, n.d.
  • [20] Shiro T, Kakiguchi K, Takahashi H, Nagata H, Tobe M. Synthesis and biological evaluation of substituted imidazoquinoline derivatives as mPGES-1 inhibitors. Bioorg Med Chem. 2013; 21: 2068–2078. https://doi.org/10.1016/j.bmc.2013.01.018
  • [21] Demirbolat İ, Kulabaş N, Gürboğa M, Bingöl-Özakpınar Ö, Çiftçi G, Yelekçi K, et al. Synthesis and evaluation of antiproliferative and mPGES-1 inhibitory activities of novel carvacrol-triazole conjugates. Org Commun. 2022; 15: 356–377.
  • [22] Bülbül B, Ding K, Zhan CG, Çiftçi G, Yelekçi K, Gürboğa M, et al. Novel 1,2,4-triazoles derived from Ibuprofen: synthesis and in vitro evaluation of their mPGES-1 inhibitory and antiproliferative activity. Mol Divers. 2022:(Early Access). https://doi.org/10.1007/s11030-022-10551-0
  • [23] Erensoy G, Ding K, Zhan CG, Çiftçi G, Yelekçi K, Duracık M, et al. Synthesis, in vitro and in silico studies on novel 3-aryloxymethyl-5-[(2-oxo-2-arylethyl)sulfanyl]-1,2,4-triazoles and their oxime derivatives as potent inhibitors of mPGES-1. J Mol Struct. 2023; 1272: 134154. https://doi.org/10.1016/j.molstruc.2022.134154
  • [24] Di Micco S, Terracciano S, Cantone V, Fischer K, Koeberle A, Foglia A, et al. Discovery of new potent molecular entities able to inhibit mPGES-1. Eur J Med Chem. 2018; 143: 1419–1427. https://doi.org/10.1016/J.EJMECH.2017.10.039
  • [25] Xia Z, Yan A. Computational models for the classification of mPGES-1 inhibitors with fingerprint descriptors. Mol Divers. 2017; 21: 661–675. https://doi.org/10.1007/s11030-017-9743-x
  • [26] Tatar E, Küçükgüzel I, Clercq E De, Şahin F, Güllüce M. Synthesis, characterization and screening of antimicrobial, antituberculosis, antiviral and anticancer activity of novel. Arkivoc 2008; 14: 191–210.
  • [27] Tatar E, Küçükgüzel İ. Synthesis, anti-tuberculosis and antiviral activity of novel 2-isonicotinoylhydrazono-5-arylidene-4-thiazolidinones. Int J Drug Des Discov 2010; 1: 19–32.
  • [28] Rahim F, Zaman K, Ullah H, Taha M, Wadood A, Javed MT, et al. Synthesis of 4-thiazolidinone analogs as potent in vitro anti-urease agents. Bioorg Chem 2015; 63: 123–131. https://doi.org/10.1016/j.bioorg.2015.10.005
  • [29] Kulabaş N, Özakpinar ÖB, Özsavcı D, Leyssen P, Neyts J, Küçükgüzel İ. Synthesis, characterization and biological evaluation of thioureas, acylthioureas and 4-thiazolidinones as anticancer and antiviral agents. Marmara Pharm J 2017; 21: 371–384.
  • [30] Singh S, Nayan B, Hilgenfeld R, Pastorino B, Lamballerie X De, Jayaprakash V. Thiazolidone derivatives as inhibitors of chikungunya virus. Eur J Med Chem 2015; 89: 172–178.
  • [31] Ottanà R, Maccari R, Amuso S, Wolber G, Schuster D, Herdlinger S, et al. New 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids active as protein tyrosine phosphatase inhibitors endowed with insulinomimetic effect on mouse C2C12 skeletal muscle cells. Eur J Med Chem 2012; 50: 332–343. https://doi.org/10.1016/j.ejmech.2012.02.012
  • [32] Pan B, Huang RZ, Han SQ, Qu D, Zhu ML, Wei P, Ying HJ. Design, synthesis, and antibiofilm activity of 2-arylimino-3-aryl-thiazolidine-4-ones. Bioorg Med Chem Lett 2010. https://doi.org/10.1016/j.bmcl.2010.03.013
  • [33] Rashid M, Husain A, Shaharyar M, Mishra R, Hussain A, Afzal O. Design and synthesis of pyrimidine molecules endowed with thiazolidin-4-one as new anticancer agents. Eur J Med Chem 2014; 83: 630–645. https://doi.org/10.1016/j.ejmech.2014.06.033
  • [34] Bhandari SV, Bothara KG, Patil AA, Chitre TS, Sarkate AP, Gore ST, et al. Design, synthesis and pharmacological screening of novel antihypertensive agents using hybrid approach. Bioorg Med Chem 2009. https://doi.org/10.1016/j.bmc.2008.10.032
  • [35] Çakir G, Küçükgüzel I, Guhamazumder R, Tatar E, Manvar D, Basu A, et al. Novel 4-thiazolidinones as non-nucleoside inhibitors of hepatitis C virus NS5B RNA-dependent RNA polymerase. Arch Pharm (Weinheim) 2015; 348: 10–22. https://doi.org/10.1002/ardp.201400247
  • [36] Küçükgüzel I, Satılmış G, Gurukumar KR, Basu A, Tatar E, Nichols DB, et al. 2-Heteroarylimino-5-arylidene-4-thiazolidinones as a new class of non-nucleoside inhibitors of HCV NS5B polymerase. Eur J Med Chem 2013; 69: 931–941. https://doi.org/10.1016/j.ejmech.2013.08.043
  • [37] Manvar D, Küçükgüzel I, Erensoy G, Tatar E, Deryabaşoʇullari G, Reddy H, et al. Discovery of conjugated thiazolidinone-thiadiazole scaffold as anti-dengue virus polymerase inhibitors. Biochem Biophys Res Commun 2016; 469: 743–747. https://doi.org/10.1016/j.bbrc.2015.12.042
  • [38] Türe A, Ergül M, Ergül M, Altun A, Küçükgüzel İ. Design, synthesis, and anticancer activity of novel 4-thiazolidinone-phenylaminopyrimidine hybrids. Mol Divers 2021; 25: 1025–1050. https://doi.org/10.1007/s11030-020-10087-1
  • [39] Tatar E, Küçükgüzel I, Kaushik-Basu N. Synthesis, characterization and antiviral evaluation of 1,3-thiazolidine-4-one derivatives bearing L-Valine side chain. Marmara Pharm J 2012; 3: 181–193. https://doi.org/10.12991/201216397
  • [40] Omar K, Geronikaki A, Zoumpoulakis P, Camoutsis C, Soković M, Cirić A, et al. Novel 4-thiazolidinone derivatives as potential antifungal and antibacterial drugs. Bioorg Med Chem 2010; 18: 426–432. https://doi.org/10.1016/j.bmc.2009.10.041
  • [41] Zhou H, Wu S, Zhai S, Liu A, Sun Y, Li R, et al. Design, synthesis, cytoselective toxicity, structure-activity relationships, and pharmacophore of thiazolidinone derivatives targeting drug-resistant lung cancer cells. J Med Chem 2008; 51: 1242–1251. https://doi.org/10.1021/jm7012024
  • [42] Eleftheriou P, Geronikaki A, Hadjipavlou-Litina D, Vicini P, Filz O, Filimonov D, et al. Fragment-based design, docking, synthesis, biological evaluation and structure-activity relationships of 2-benzo/benzisothiazolimino-5-aryliden-4-thiazolidinones as cyclooxygenase/lipoxygenase inhibitors. Eur J Med Chem 2012; 47: 111–124. https://doi.org/10.1016/j.ejmech.2011.10.029
  • [43] He S, Li C, Liu Y, Lai L. Discovery of highly potent microsomal prostaglandin E2 synthase 1 inhibitors using the active conformation structural model and virtual screen. J Med Chem 2013; 56: 3296–3309. https://doi.org/10.1021/jm301900x
  • [44] Colarusso E, Potenza M, Lauro G, Chini MG, Sepe V, Zampella A, et al. Thiazolidin-4-one-based compounds interfere with the eicosanoid biosynthesis pathways by mPGES-1/sEH/5-LO multi-target inhibition. Eur J Med Chem Reports 2022; 5: 1–14. https://doi.org/10.1016/j.ejmcr.2022.100046
  • [45] Khurana P, Jachak SM. Chemistry and biology of microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors as novel anti-inflammatory agents: recent developments and current status. RSC Adv 2016; 6: 28343–28369.
  • [46] Trott O, Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010; 31: 455–461. https://doi.org/10.1002/jcc.21334
  • [47] 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: 2785–2791. https://doi.org/10.1002/jcc.21256
  • [48] Wang JL, Limburg D, Graneto MJ, Springer J, Hamper JRB, Liao S, et al. The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: The second clinical candidate having a shorter and favorable human half-life. Bioorg Med Chem Lett 2010; 20: 7159–7163. https://doi.org/10.1016/J.BMCL.2010.07.054
  • [49] 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: 1–13. https://doi.org/10.1038/srep42717

Yıl 2023, Cilt: 27 Sayı: 5, 2124 - 2134, 28.06.2025

Necla Kulabaş

Öz

Kaynakça

  • [1] Al-Turki DA, Abou-Zeid LA, Shehata LA, Al-Omar MA. Therapeutic and Toxic Effects of New NSAIDs and Related Compounds: A Review and Prospective Study. Int J Pharmacol. 2010; 6: 813–825.
  • [2] Hassan GS, Abou-Seri SM, Kamel G, Ali MM. Celecoxib analogs bearing benzofuran moiety as cyclooxygenase-2 inhibitors: Design, synthesis and evaluation as potential anti-inflammatory agents. Eur J Med Chem. 2014; 76: 482–493. https://doi.org/10.1016/j.ejmech.2014.02.033
  • [3] Basile L, Alvarez S, Blanco A, Santagati A, Granata G, Di Pietro P, Guccione S, Muñoz-Fernández MÁ. Sulfonilamidothiopyrimidone and thiopyrimidone derivatives as selective COX-2 inhibitors: synthesis, biological evaluation, and docking studies. Eur J Med Chem. 2012; 57: 149–161. https://doi.org/10.1016/j.ejmech.2012.09.005
  • [4] Chen WC, Tseng CK, Chen YH, Lin CK, Hsu S, Wang SN, Lee JC. HCV NS5A up-regulates COX-2 expression via IL-8-mediated activation of the ERK/JNK MAPK pathway. PLoS One. 2015; 10: 1–21. https://doi.org/10.1371/journal.pone.0133264
  • [5] Sjögren T, Nord J, Ek M, Johansson P, Liu G, Geschwindner S. Crystal structure of microsomal prostaglandin E2 synthase provides insight into diversity in the MAPEG superfamily. Proc Natl Acad Sci U S A. 2013; 110: 3806–3811. https://doi.org/10.1073/pnas.1218504110
  • [6] Akasaka H, So SP, Ruan KH. Relationship of the Topological Distances and Activities between mPGES-1 and COX-2 versus COX-1: Implications of the Different Post-Translational Endoplasmic Reticulum Organizations of COX-1 and COX-2. Biochemistry. 2015; 54: 3707–3715. https://doi.org/10.1021/acs.biochem.5b00339
  • [7] Perry LA, Mosler C, Atkins A, Minehart M. Cardiovascular Risk Associated With NSAIDs and COX-2 Inhibitors. US Pharm. 2014; 39: 35–38.
  • [8] Muthukaman N, Deshmukh S, Tambe M, Pisal D, Tondlekar S, Shaikh M, et al. Alleviating CYP and hERG liabilities by structure optimization of dihydrofuran-fused tricyclic benzo[d]imidazole series – Potent, selective and orally efficacious microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors: Part-2. Bioorg Med Chem Lett. 2018; 28: 1211–1218. https://doi.org/10.1016/j.bmcl.2018.02.048
  • [9] Ding K, Zhou Z, Zhou S, Yuan Y, Kim K, Zhang T, Zheng X, Zheng F, Zhan CG. Design, synthesis, and discovery of 5-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-triones and related derivatives as novel inhibitors of mPGES-1. Bioorg Med Chem Lett. 2018; 28: 858–862. https://doi.org/10.1016/j.bmcl.2018.02.011
  • [10] Ding K, Zhou Z, Hou S, Yuan Y, Zhou S, Zheng X, Chen J, Loftin C, Zheng F, Zhan C-G. Structure-based discovery of mPGES-1 inhibitors suitable for preclinical testing in wild-type mice as a new generation of anti-inflammatory drugs. Sci Rep. 2018; 8: 5205. https://doi.org/10.1038/s41598-018-23482-4
  • [11] Koeberle A, Werz O. Perspective of microsomal prostaglandin E2 synthase-1 as drug target in inflammation-related disorders. Biochem Pharmacol. 2015; 98: 1–15. https://doi.org/10.1016/j.bcp.2015.06.022
  • [12] Koeberle A, Laufer SA, Werz O. Design and Development of Microsomal Prostaglandin E2 Synthase-1 Inhibitors: Challenges and Future Directions. J Med Chem. 2016; 59: 5970–5986. https://doi.org/10.1021/acs.jmedchem.5b01750
  • [13] Mancini JA, Blood K, Guay J, Gordon R, Claveau D, Chan CC, Riendeau D. Cloning, Expression, and Up-regulation of Inducible Rat Prostaglandin E Synthase during Lipopolysaccharide-induced Pyresis and Adjuvant-induced Arthritis. J Biol Chem. 2001; 276: 4469–4475. https://doi.org/10.1074/jbc.M006865200
  • [14] Xu D, Rowland SE, Clark P, Giroux A, Côté B, Guiral S, et al. MF63 [2-(6-chloro-1H-phenanthro[9,10-d]imidazol-2-yl)-isophthalonitrile], a selective microsomal prostaglandin E synthase-1 inhibitor, relieves pyresis and pain in preclinical models of inflammation. J Pharmacol Exp Ther. 2008; 326: 754–763. https://doi.org/10.1124/jpet.108.138776
  • [15] Arhancet GB, Walker DP, Metz S, Fobian YM, Heasley SE, Carter JS, et al. Discovery and SAR of PF-4693627, a potent, selective and orally bioavailable mPGES-1 inhibitor for the potential treatment of inflammation. Bioorg Med Chem Lett. 2013; 23: 1114–1119. https://doi.org/10.1016/j.bmcl.2012.11.109
  • [16] Banerjee A, Pawar MY, Patil S, Yadav PS, Kadam PA, Kattige VG, et al. Development of 2-aryl substituted quinazolin-4(3H)-one, pyrido[4,3-d]pyrimidin-4(3H)-one and pyrido[2,3-d]pyrimidin-4(3H)-one derivatives as microsomal prostaglandin E2 synthase-1 inhibitors. Bioorg Med Chem Lett. 2014; 24: 4838–4844. https://doi.org/10.1016/j.bmcl.2014.08.056
  • [17] Schiffler MA, Antonysamy S, Bhattachar SN, Campanale KM, Chandrasekhar S, Condon B, et al. Discovery and Characterization of 2-Acylaminoimidazole Microsomal Prostaglandin E Synthase-1 Inhibitors. J Med Chem. 2016; 59: 194–205. https://doi.org/10.1021/acs.jmedchem.5b01249
  • [18] Wannberg J. Piperidinyl benzoimidazole derivatives as mPGES-1 inhibitors. US Patent 2016/0122330 A1, 2016.
  • [19] Priepke H, Doods H, Kuelzer R, Pfau R. 3H-imidazo[4,5-C]pyridine-6-carboxamides as anti-inflammatory agents. US Patent US8759537B2, n.d.
  • [20] Shiro T, Kakiguchi K, Takahashi H, Nagata H, Tobe M. Synthesis and biological evaluation of substituted imidazoquinoline derivatives as mPGES-1 inhibitors. Bioorg Med Chem. 2013; 21: 2068–2078. https://doi.org/10.1016/j.bmc.2013.01.018
  • [21] Demirbolat İ, Kulabaş N, Gürboğa M, Bingöl-Özakpınar Ö, Çiftçi G, Yelekçi K, et al. Synthesis and evaluation of antiproliferative and mPGES-1 inhibitory activities of novel carvacrol-triazole conjugates. Org Commun. 2022; 15: 356–377.
  • [22] Bülbül B, Ding K, Zhan CG, Çiftçi G, Yelekçi K, Gürboğa M, et al. Novel 1,2,4-triazoles derived from Ibuprofen: synthesis and in vitro evaluation of their mPGES-1 inhibitory and antiproliferative activity. Mol Divers. 2022:(Early Access). https://doi.org/10.1007/s11030-022-10551-0
  • [23] Erensoy G, Ding K, Zhan CG, Çiftçi G, Yelekçi K, Duracık M, et al. Synthesis, in vitro and in silico studies on novel 3-aryloxymethyl-5-[(2-oxo-2-arylethyl)sulfanyl]-1,2,4-triazoles and their oxime derivatives as potent inhibitors of mPGES-1. J Mol Struct. 2023; 1272: 134154. https://doi.org/10.1016/j.molstruc.2022.134154
  • [24] Di Micco S, Terracciano S, Cantone V, Fischer K, Koeberle A, Foglia A, et al. Discovery of new potent molecular entities able to inhibit mPGES-1. Eur J Med Chem. 2018; 143: 1419–1427. https://doi.org/10.1016/J.EJMECH.2017.10.039
  • [25] Xia Z, Yan A. Computational models for the classification of mPGES-1 inhibitors with fingerprint descriptors. Mol Divers. 2017; 21: 661–675. https://doi.org/10.1007/s11030-017-9743-x
  • [26] Tatar E, Küçükgüzel I, Clercq E De, Şahin F, Güllüce M. Synthesis, characterization and screening of antimicrobial, antituberculosis, antiviral and anticancer activity of novel. Arkivoc 2008; 14: 191–210.
  • [27] Tatar E, Küçükgüzel İ. Synthesis, anti-tuberculosis and antiviral activity of novel 2-isonicotinoylhydrazono-5-arylidene-4-thiazolidinones. Int J Drug Des Discov 2010; 1: 19–32.
  • [28] Rahim F, Zaman K, Ullah H, Taha M, Wadood A, Javed MT, et al. Synthesis of 4-thiazolidinone analogs as potent in vitro anti-urease agents. Bioorg Chem 2015; 63: 123–131. https://doi.org/10.1016/j.bioorg.2015.10.005
  • [29] Kulabaş N, Özakpinar ÖB, Özsavcı D, Leyssen P, Neyts J, Küçükgüzel İ. Synthesis, characterization and biological evaluation of thioureas, acylthioureas and 4-thiazolidinones as anticancer and antiviral agents. Marmara Pharm J 2017; 21: 371–384.
  • [30] Singh S, Nayan B, Hilgenfeld R, Pastorino B, Lamballerie X De, Jayaprakash V. Thiazolidone derivatives as inhibitors of chikungunya virus. Eur J Med Chem 2015; 89: 172–178.
  • [31] Ottanà R, Maccari R, Amuso S, Wolber G, Schuster D, Herdlinger S, et al. New 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids active as protein tyrosine phosphatase inhibitors endowed with insulinomimetic effect on mouse C2C12 skeletal muscle cells. Eur J Med Chem 2012; 50: 332–343. https://doi.org/10.1016/j.ejmech.2012.02.012
  • [32] Pan B, Huang RZ, Han SQ, Qu D, Zhu ML, Wei P, Ying HJ. Design, synthesis, and antibiofilm activity of 2-arylimino-3-aryl-thiazolidine-4-ones. Bioorg Med Chem Lett 2010. https://doi.org/10.1016/j.bmcl.2010.03.013
  • [33] Rashid M, Husain A, Shaharyar M, Mishra R, Hussain A, Afzal O. Design and synthesis of pyrimidine molecules endowed with thiazolidin-4-one as new anticancer agents. Eur J Med Chem 2014; 83: 630–645. https://doi.org/10.1016/j.ejmech.2014.06.033
  • [34] Bhandari SV, Bothara KG, Patil AA, Chitre TS, Sarkate AP, Gore ST, et al. Design, synthesis and pharmacological screening of novel antihypertensive agents using hybrid approach. Bioorg Med Chem 2009. https://doi.org/10.1016/j.bmc.2008.10.032
  • [35] Çakir G, Küçükgüzel I, Guhamazumder R, Tatar E, Manvar D, Basu A, et al. Novel 4-thiazolidinones as non-nucleoside inhibitors of hepatitis C virus NS5B RNA-dependent RNA polymerase. Arch Pharm (Weinheim) 2015; 348: 10–22. https://doi.org/10.1002/ardp.201400247
  • [36] Küçükgüzel I, Satılmış G, Gurukumar KR, Basu A, Tatar E, Nichols DB, et al. 2-Heteroarylimino-5-arylidene-4-thiazolidinones as a new class of non-nucleoside inhibitors of HCV NS5B polymerase. Eur J Med Chem 2013; 69: 931–941. https://doi.org/10.1016/j.ejmech.2013.08.043
  • [37] Manvar D, Küçükgüzel I, Erensoy G, Tatar E, Deryabaşoʇullari G, Reddy H, et al. Discovery of conjugated thiazolidinone-thiadiazole scaffold as anti-dengue virus polymerase inhibitors. Biochem Biophys Res Commun 2016; 469: 743–747. https://doi.org/10.1016/j.bbrc.2015.12.042
  • [38] Türe A, Ergül M, Ergül M, Altun A, Küçükgüzel İ. Design, synthesis, and anticancer activity of novel 4-thiazolidinone-phenylaminopyrimidine hybrids. Mol Divers 2021; 25: 1025–1050. https://doi.org/10.1007/s11030-020-10087-1
  • [39] Tatar E, Küçükgüzel I, Kaushik-Basu N. Synthesis, characterization and antiviral evaluation of 1,3-thiazolidine-4-one derivatives bearing L-Valine side chain. Marmara Pharm J 2012; 3: 181–193. https://doi.org/10.12991/201216397
  • [40] Omar K, Geronikaki A, Zoumpoulakis P, Camoutsis C, Soković M, Cirić A, et al. Novel 4-thiazolidinone derivatives as potential antifungal and antibacterial drugs. Bioorg Med Chem 2010; 18: 426–432. https://doi.org/10.1016/j.bmc.2009.10.041
  • [41] Zhou H, Wu S, Zhai S, Liu A, Sun Y, Li R, et al. Design, synthesis, cytoselective toxicity, structure-activity relationships, and pharmacophore of thiazolidinone derivatives targeting drug-resistant lung cancer cells. J Med Chem 2008; 51: 1242–1251. https://doi.org/10.1021/jm7012024
  • [42] Eleftheriou P, Geronikaki A, Hadjipavlou-Litina D, Vicini P, Filz O, Filimonov D, et al. Fragment-based design, docking, synthesis, biological evaluation and structure-activity relationships of 2-benzo/benzisothiazolimino-5-aryliden-4-thiazolidinones as cyclooxygenase/lipoxygenase inhibitors. Eur J Med Chem 2012; 47: 111–124. https://doi.org/10.1016/j.ejmech.2011.10.029
  • [43] He S, Li C, Liu Y, Lai L. Discovery of highly potent microsomal prostaglandin E2 synthase 1 inhibitors using the active conformation structural model and virtual screen. J Med Chem 2013; 56: 3296–3309. https://doi.org/10.1021/jm301900x
  • [44] Colarusso E, Potenza M, Lauro G, Chini MG, Sepe V, Zampella A, et al. Thiazolidin-4-one-based compounds interfere with the eicosanoid biosynthesis pathways by mPGES-1/sEH/5-LO multi-target inhibition. Eur J Med Chem Reports 2022; 5: 1–14. https://doi.org/10.1016/j.ejmcr.2022.100046
  • [45] Khurana P, Jachak SM. Chemistry and biology of microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors as novel anti-inflammatory agents: recent developments and current status. RSC Adv 2016; 6: 28343–28369.
  • [46] Trott O, Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010; 31: 455–461. https://doi.org/10.1002/jcc.21334
  • [47] 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: 2785–2791. https://doi.org/10.1002/jcc.21256
  • [48] Wang JL, Limburg D, Graneto MJ, Springer J, Hamper JRB, Liao S, et al. The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: The second clinical candidate having a shorter and favorable human half-life. Bioorg Med Chem Lett 2010; 20: 7159–7163. https://doi.org/10.1016/J.BMCL.2010.07.054
  • [49] 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: 1–13. https://doi.org/10.1038/srep42717
Toplam 49 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Farmasotik Kimya
Bölüm Articles
Yazarlar

Necla Kulabaş 0000-0003-2273-5094

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2023 Cilt: 27 Sayı: 5

Kaynak Göster

APA Kulabaş, N. (2025). In silico investigation of novel 5-benzylidene-2- (arylsulfonylhydrazono)thiazolidine-4-ones as potential inhibitors of mPGES-1 and COX-2. Journal of Research in Pharmacy, 27(5), 2124-2134.
AMA Kulabaş N. In silico investigation of novel 5-benzylidene-2- (arylsulfonylhydrazono)thiazolidine-4-ones as potential inhibitors of mPGES-1 and COX-2. J. Res. Pharm. Temmuz 2025;27(5):2124-2134.
Chicago Kulabaş, Necla. “In Silico Investigation of Novel 5-Benzylidene-2- (arylsulfonylhydrazono)thiazolidine-4-Ones As Potential Inhibitors of MPGES-1 and COX-2”. Journal of Research in Pharmacy 27, sy. 5 (Temmuz 2025): 2124-34.
EndNote Kulabaş N (01 Temmuz 2025) In silico investigation of novel 5-benzylidene-2- (arylsulfonylhydrazono)thiazolidine-4-ones as potential inhibitors of mPGES-1 and COX-2. Journal of Research in Pharmacy 27 5 2124–2134.
IEEE N. Kulabaş, “In silico investigation of novel 5-benzylidene-2- (arylsulfonylhydrazono)thiazolidine-4-ones as potential inhibitors of mPGES-1 and COX-2”, J. Res. Pharm., c. 27, sy. 5, ss. 2124–2134, 2025.
ISNAD Kulabaş, Necla. “In Silico Investigation of Novel 5-Benzylidene-2- (arylsulfonylhydrazono)thiazolidine-4-Ones As Potential Inhibitors of MPGES-1 and COX-2”. Journal of Research in Pharmacy 27/5 (Temmuz 2025), 2124-2134.
JAMA Kulabaş N. In silico investigation of novel 5-benzylidene-2- (arylsulfonylhydrazono)thiazolidine-4-ones as potential inhibitors of mPGES-1 and COX-2. J. Res. Pharm. 2025;27:2124–2134.
MLA Kulabaş, Necla. “In Silico Investigation of Novel 5-Benzylidene-2- (arylsulfonylhydrazono)thiazolidine-4-Ones As Potential Inhibitors of MPGES-1 and COX-2”. Journal of Research in Pharmacy, c. 27, sy. 5, 2025, ss. 2124-3.
Vancouver Kulabaş N. In silico investigation of novel 5-benzylidene-2- (arylsulfonylhydrazono)thiazolidine-4-ones as potential inhibitors of mPGES-1 and COX-2. J. Res. Pharm. 2025;27(5):2124-3.