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Synthesis and potential antitumor activities of mandelic acid linked 2-aryl-1,3-thiazolidin-4-ones

Yıl 2022, Cilt: 26 Sayı: 4, 931 - 940, 28.06.2025

Kübra Demir-yazıcı , Özlen Güzel Akdemir

Öz

In our pursuit to discover new anticancer agents, we have synthesized a new series of 2-aryl-1,3-
thiazolidin-4-one derivatives carrying a mandelic acid part. Compounds 3a-h and 4a-j have been synthesized with the
cyclization of mandelic acid-derived Schiff bases, their structures have been elucidated with spectral methods (1H-NMR,
13C-NMR, and LC/MS-APCI) and elemental analyzes (C, H, N). Five compounds 3d, 3e, 4e, 4f, and 4g chosen as
prototypes were evaluated against the full panel of 58 human tumor cell lines in the National Cancer Institute’s in vitro
primary cytotoxicity assay (Bethesda, Maryland). Among the tested compound, 3e showed good cytotoxic effects
against melanoma cell line UACC-62. Compounds 3d, 4e, 4f, and 4g showed moderate cytotoxic effects, especially
against leukemia cell line, RPMI-8226, non-small cell lung cancer cell lines NCI-H23 and HOP-92, central nervous
system (CNS) cancer cell lines SF-295 and SNB-75, melanoma cell line UACC-62, and ovarian cancer cell line IGROV1.
It is considered that the in vitro test results of selected compounds are promising and an additional mandelic acid moiety
to core structure 2-aryl-1,3-thiazolidin-4-one and different modifications may result in effective agents in anticancer
treatment.

Anahtar Kelimeler

1 3-Thiazolidin-4-one mandelic acid synthesis anticancer agents in vitro cytotoxicity assay

Kaynakça

  • [1] Krieghoff-Henning E, Folkerts J, Penzkofer A, Weg-Remers S. Cancer – an overview. Med Monatsschr Pharm.2017; 40(2): 48—54.
  • [2] Peate I. Understanding cancer. Br J Healthc Assist. 2018; 12(7): 350–355. [CrossRef]
  • [3] Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, Bray F. Cancer statistics for the year 2020: An overview. Int J Cancer 2021; 149(4): 778–789. [CrossRef]
  • [4] Gottesman MM. Mechanisms of cancer drug resistance. Annu Rev Med. 2002; 53: 615–627. [CrossRef]
  • [5] Nikolaou M, Pavlopoulou A, Georgakilas AG, Kyrodimos E. The challenge of drug resistance in cancer treatment: a current overview. Clin Exp Metastasis 2018; 35(4): 309–318. [CrossRef]
  • [6] Love RR, Leventhal H, Easterling D V, Nerenz DR. Side effects and emotional distress during cancer chemotherapy. Cancer 1989; 63(3): 604–612. [CrossRef]
  • [7] Samadhiya P, Sharma R, Srivastava SK, Srivastava SD. Synthesis and biological evaluation of 4-thiazolidinonederivatives as antitubercular and antimicrobial agents. Arab J Chem. 2014; 7(5): 657–665. [CrossRef]
  • [8] Desai NC, Jadeja KA, Jadeja DJ, Khedkar VM, Jha PC. Design, synthesis, antimicrobial evaluation, and molecular docking study of some 4-thiazolidinone derivatives containing pyridine and quinazoline moiety. Synth Commun. 2021; 51(6): 952–963. [CrossRef]
  • [9] De Oliveira Filho GB, De Oliveira Cardoso MV, Espíndola JWP, Ferreira LFGR, De Simone CA, Ferreira RS, Coelho PL, Meira CS, Magalhaes Moreira DR, Soares MBP, Lima Leite AC. Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi. Bioorganic Med Chem. 2015; 23(23): 7478–7486. [CrossRef]
  • [10] Omar K, Geronikaki A, Zoumpoulakis P, Camoutsis C, Soković M, Ćirić A, Glamočlija J. Novel 4-thiazolidinone derivatives as potential antifungal and antibacterial drugs. Bioorganic Med Chem. 2010; 18(1): 426–432. [CrossRef]
  • [11] Barbosa VA, Baréa P, Mazia RS, Ueda-Nakamura T, Costa WF da, Foglio MA, Goes Ruiz ALT, Carvalho JE de, Vendramini–Costa DB, Nakamura CV, Sarragiotto MH. Synthesis and evaluation of novel hybrids β-carboline-4- thiazolidinones as potential antitumor and antiviral agents. Eur J Med Chem. 2016; 124: 1093–1104. [CrossRef]
  • [12] Çakir G, Küҫ ükgüzel I, Guhamazumder R, Tatar E, Manvar D, Basu A, Patel BA, Zia J, Talele TT, Kaushik-Basu N. Novel 4-thiazolidinones as non-nucleoside inhibitors of hepatitis C virus NS5B RNA-dependent RNA polymerase. Arch Pharm (Weinheim). 2015; 348(1): 10–22. [CrossRef]
  • [13] Szychowski KA, Kaminskyy D V., Leja ML, Kryshchyshyn AP, Lesyk RB, Tobiasz J, Wnuk M, Pomianek T, Gmiński J. Anticancer properties of 5Z-(4-fluorobenzylidene)-2-(4-hydroxyphenylamino)-thiazol-4-one. Sci Rep. 2019; 9(1): 1–16. [CrossRef]
  • [14] 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(2): 1025–1050. [CrossRef]
  • [15] Güzel-Akdemir Ö, Demir-Yazici K. Benzilic acid based new 2-aryl-1,3-thiazolidin-4-one derivatives: Synthesis and anticancer activity. J Res Pharm. 2021; 25(3): 305–317. [CrossRef]
  • [16] Güzel-Akdemir Ö, Trawally M, Özbek-Babuç M, Özbek-Çelik B, Ermut G, Özdemir H. Synthesis and antibacterial activity of new hybrid derivatives of 5-sulfamoyl-1H-indole and 4-thiazolidinone groups. Monatsh Chem. 2020; 151(9): 1443–1452. [CrossRef]
  • [17] Güzel-Akdemir Ö, Angeli A, Demir K, Supuran CT, Akdemir A. Novel thiazolidinone-containing compounds, without the well-known sulphonamide zinc-binding group acting as human carbonic anhydrase IX inhibitors. J Enzyme Inhib Med Chem. 2018; 33(1): 1299–1308. [CrossRef]
  • [18] Güzel-Akdemir Ö, Carradori S, Grande R, Demir-Yazıcı K, Angeli A, Supuran CT, Akdemir A. Development of thiazolidinones as fungal carbonic anhydrase inhibitors. Int J Mol Sci. 2020; 21(8): 2960. [CrossRef]
  • [19] Güzel-Akdemir Ö, Demir-Yazici K, Trawally M, Dingiş-Birgül SI, Akdemir A. Evaluation of new 2-hydroxy-N- (4-oxo-2-substituted phenyl-1,3-thiazolidin-3-yl)-2-phenylacetamide derivatives as potential antimycobacterial agents. Org Commun. 2020; 13(2): 33–50. [CrossRef]
  • [20] Güzel Ö, Ilhan E, Salman A. Synthesis and antimycobacterial activity of new 2-hydroxy-N-(3-oxo-1-thia- 4- azaspiro[4.4]non-4-yl)/(3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl)-2, 2-diphenylacetamide derivatives. Monatsh Chem. 2006; 137(6): 795–801. [CrossRef]
  • [21] Güzel Ö, Salman A. Synthesis and biological evaluation of new 4-thiazolidinone derivatives. J Enzyme Inhib Med Chem. 2009; 24(4): 1015–1023. [CrossRef]
  • [22] Güzel Ö, Terzioǧ lu N, Çapan G, Salman A. Synthesis and biological evaluation of new 5-methyl-N-(3-oxo-1-thia- 4- azaspiro[4.5]-dec-4-yl)-3-phenyl-1H-indole-2-carboxamide derivatives. Arkivoc. 2006; 2006(12): 98–110.
  • [23] Kaynak FB, Öztürk D, Özbey S, Çapan G. New N′-alkylidene/cycloalkylidene derivatives of 5-methyl-3-phenylDemir- 1H-indole-2-carbohydrazide: Synthesis, crystal structure, and quantum mechanical calculations. J Mol Struct. 2005; 740(1–3): 213–221. [CrossRef]
  • [24] Taylor PJ. The infra-red spectroscopy of some 2-substituted thiazolid-4-ones, a new class of enamino-ketone-II . Infra-red assigments and chemical implications. Spectrochim Acta Part A Mol Spectrosc. 1970; 26(1): 165–194. [CrossRef]
  • [25] Küçükgüzel ŞG, Oruç EE, Rollas S, Şahin F, Özbek A. Synthesis, characterisation and biological activity of novel 4-thiazolidinones, 1,3,4-oxadiazoles and some related compounds. Eur J Med Chem. 2002; 37(3): 197–206. [CrossRef]
  • [26] Verma A, Saraf SK. 4-Thiazolidinone - A biologically active scaffold. Eur J Med Chem. 2008; 43(5): 897–905. [CrossRef]
  • [27] Boyd MR, Paull KD. Some practical considerations and applications of the national cancer institute in vitro anticancer drug discovery screen. Drug Dev Res. 1995; 34(2): 91–109. [CrossRef]
  • [28] Grever MR, Schepartz SA CB, Grever MR, Schepartz SA, Chabner BA. The National Cancer Institute: Cancer drug discovery and development program. Semin Oncol. 1992; 19(6): 622.
  • [29] Zieliński W, Kudelko A, Czardybon W. The synthesis of 4-acylamino-1,2,4-triazole derivatives in the reaction of α-hydroxyacid hydrazides and orthoesters. J Heterocycl Chem. 2005; 42(7): 1393–1397. [CrossRef]

Yıl 2022, Cilt: 26 Sayı: 4, 931 - 940, 28.06.2025

Kübra Demir-yazıcı , Özlen Güzel Akdemir

Öz

Kaynakça

  • [1] Krieghoff-Henning E, Folkerts J, Penzkofer A, Weg-Remers S. Cancer – an overview. Med Monatsschr Pharm.2017; 40(2): 48—54.
  • [2] Peate I. Understanding cancer. Br J Healthc Assist. 2018; 12(7): 350–355. [CrossRef]
  • [3] Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, Bray F. Cancer statistics for the year 2020: An overview. Int J Cancer 2021; 149(4): 778–789. [CrossRef]
  • [4] Gottesman MM. Mechanisms of cancer drug resistance. Annu Rev Med. 2002; 53: 615–627. [CrossRef]
  • [5] Nikolaou M, Pavlopoulou A, Georgakilas AG, Kyrodimos E. The challenge of drug resistance in cancer treatment: a current overview. Clin Exp Metastasis 2018; 35(4): 309–318. [CrossRef]
  • [6] Love RR, Leventhal H, Easterling D V, Nerenz DR. Side effects and emotional distress during cancer chemotherapy. Cancer 1989; 63(3): 604–612. [CrossRef]
  • [7] Samadhiya P, Sharma R, Srivastava SK, Srivastava SD. Synthesis and biological evaluation of 4-thiazolidinonederivatives as antitubercular and antimicrobial agents. Arab J Chem. 2014; 7(5): 657–665. [CrossRef]
  • [8] Desai NC, Jadeja KA, Jadeja DJ, Khedkar VM, Jha PC. Design, synthesis, antimicrobial evaluation, and molecular docking study of some 4-thiazolidinone derivatives containing pyridine and quinazoline moiety. Synth Commun. 2021; 51(6): 952–963. [CrossRef]
  • [9] De Oliveira Filho GB, De Oliveira Cardoso MV, Espíndola JWP, Ferreira LFGR, De Simone CA, Ferreira RS, Coelho PL, Meira CS, Magalhaes Moreira DR, Soares MBP, Lima Leite AC. Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi. Bioorganic Med Chem. 2015; 23(23): 7478–7486. [CrossRef]
  • [10] Omar K, Geronikaki A, Zoumpoulakis P, Camoutsis C, Soković M, Ćirić A, Glamočlija J. Novel 4-thiazolidinone derivatives as potential antifungal and antibacterial drugs. Bioorganic Med Chem. 2010; 18(1): 426–432. [CrossRef]
  • [11] Barbosa VA, Baréa P, Mazia RS, Ueda-Nakamura T, Costa WF da, Foglio MA, Goes Ruiz ALT, Carvalho JE de, Vendramini–Costa DB, Nakamura CV, Sarragiotto MH. Synthesis and evaluation of novel hybrids β-carboline-4- thiazolidinones as potential antitumor and antiviral agents. Eur J Med Chem. 2016; 124: 1093–1104. [CrossRef]
  • [12] Çakir G, Küҫ ükgüzel I, Guhamazumder R, Tatar E, Manvar D, Basu A, Patel BA, Zia J, Talele TT, Kaushik-Basu N. Novel 4-thiazolidinones as non-nucleoside inhibitors of hepatitis C virus NS5B RNA-dependent RNA polymerase. Arch Pharm (Weinheim). 2015; 348(1): 10–22. [CrossRef]
  • [13] Szychowski KA, Kaminskyy D V., Leja ML, Kryshchyshyn AP, Lesyk RB, Tobiasz J, Wnuk M, Pomianek T, Gmiński J. Anticancer properties of 5Z-(4-fluorobenzylidene)-2-(4-hydroxyphenylamino)-thiazol-4-one. Sci Rep. 2019; 9(1): 1–16. [CrossRef]
  • [14] 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(2): 1025–1050. [CrossRef]
  • [15] Güzel-Akdemir Ö, Demir-Yazici K. Benzilic acid based new 2-aryl-1,3-thiazolidin-4-one derivatives: Synthesis and anticancer activity. J Res Pharm. 2021; 25(3): 305–317. [CrossRef]
  • [16] Güzel-Akdemir Ö, Trawally M, Özbek-Babuç M, Özbek-Çelik B, Ermut G, Özdemir H. Synthesis and antibacterial activity of new hybrid derivatives of 5-sulfamoyl-1H-indole and 4-thiazolidinone groups. Monatsh Chem. 2020; 151(9): 1443–1452. [CrossRef]
  • [17] Güzel-Akdemir Ö, Angeli A, Demir K, Supuran CT, Akdemir A. Novel thiazolidinone-containing compounds, without the well-known sulphonamide zinc-binding group acting as human carbonic anhydrase IX inhibitors. J Enzyme Inhib Med Chem. 2018; 33(1): 1299–1308. [CrossRef]
  • [18] Güzel-Akdemir Ö, Carradori S, Grande R, Demir-Yazıcı K, Angeli A, Supuran CT, Akdemir A. Development of thiazolidinones as fungal carbonic anhydrase inhibitors. Int J Mol Sci. 2020; 21(8): 2960. [CrossRef]
  • [19] Güzel-Akdemir Ö, Demir-Yazici K, Trawally M, Dingiş-Birgül SI, Akdemir A. Evaluation of new 2-hydroxy-N- (4-oxo-2-substituted phenyl-1,3-thiazolidin-3-yl)-2-phenylacetamide derivatives as potential antimycobacterial agents. Org Commun. 2020; 13(2): 33–50. [CrossRef]
  • [20] Güzel Ö, Ilhan E, Salman A. Synthesis and antimycobacterial activity of new 2-hydroxy-N-(3-oxo-1-thia- 4- azaspiro[4.4]non-4-yl)/(3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl)-2, 2-diphenylacetamide derivatives. Monatsh Chem. 2006; 137(6): 795–801. [CrossRef]
  • [21] Güzel Ö, Salman A. Synthesis and biological evaluation of new 4-thiazolidinone derivatives. J Enzyme Inhib Med Chem. 2009; 24(4): 1015–1023. [CrossRef]
  • [22] Güzel Ö, Terzioǧ lu N, Çapan G, Salman A. Synthesis and biological evaluation of new 5-methyl-N-(3-oxo-1-thia- 4- azaspiro[4.5]-dec-4-yl)-3-phenyl-1H-indole-2-carboxamide derivatives. Arkivoc. 2006; 2006(12): 98–110.
  • [23] Kaynak FB, Öztürk D, Özbey S, Çapan G. New N′-alkylidene/cycloalkylidene derivatives of 5-methyl-3-phenylDemir- 1H-indole-2-carbohydrazide: Synthesis, crystal structure, and quantum mechanical calculations. J Mol Struct. 2005; 740(1–3): 213–221. [CrossRef]
  • [24] Taylor PJ. The infra-red spectroscopy of some 2-substituted thiazolid-4-ones, a new class of enamino-ketone-II . Infra-red assigments and chemical implications. Spectrochim Acta Part A Mol Spectrosc. 1970; 26(1): 165–194. [CrossRef]
  • [25] Küçükgüzel ŞG, Oruç EE, Rollas S, Şahin F, Özbek A. Synthesis, characterisation and biological activity of novel 4-thiazolidinones, 1,3,4-oxadiazoles and some related compounds. Eur J Med Chem. 2002; 37(3): 197–206. [CrossRef]
  • [26] Verma A, Saraf SK. 4-Thiazolidinone - A biologically active scaffold. Eur J Med Chem. 2008; 43(5): 897–905. [CrossRef]
  • [27] Boyd MR, Paull KD. Some practical considerations and applications of the national cancer institute in vitro anticancer drug discovery screen. Drug Dev Res. 1995; 34(2): 91–109. [CrossRef]
  • [28] Grever MR, Schepartz SA CB, Grever MR, Schepartz SA, Chabner BA. The National Cancer Institute: Cancer drug discovery and development program. Semin Oncol. 1992; 19(6): 622.
  • [29] Zieliński W, Kudelko A, Czardybon W. The synthesis of 4-acylamino-1,2,4-triazole derivatives in the reaction of α-hydroxyacid hydrazides and orthoesters. J Heterocycl Chem. 2005; 42(7): 1393–1397. [CrossRef]
Toplam 29 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Farmasotik Kimya
Bölüm Articles
Yazarlar

Kübra Demir-yazıcı 0000-0001-9928-4733

Özlen Güzel Akdemir 0000-0003-3680-1945

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2022 Cilt: 26 Sayı: 4

Kaynak Göster

APA Demir-yazıcı, K., & Güzel Akdemir, Ö. (2025). Synthesis and potential antitumor activities of mandelic acid linked 2-aryl-1,3-thiazolidin-4-ones. Journal of Research in Pharmacy, 26(4), 931-940.
AMA Demir-yazıcı K, Güzel Akdemir Ö. Synthesis and potential antitumor activities of mandelic acid linked 2-aryl-1,3-thiazolidin-4-ones. J. Res. Pharm. Haziran 2025;26(4):931-940.
Chicago Demir-yazıcı, Kübra, ve Özlen Güzel Akdemir. “Synthesis and Potential Antitumor Activities of Mandelic Acid Linked 2-Aryl-1,3-Thiazolidin-4-Ones”. Journal of Research in Pharmacy 26, sy. 4 (Haziran 2025): 931-40.
EndNote Demir-yazıcı K, Güzel Akdemir Ö (01 Haziran 2025) Synthesis and potential antitumor activities of mandelic acid linked 2-aryl-1,3-thiazolidin-4-ones. Journal of Research in Pharmacy 26 4 931–940.
IEEE K. Demir-yazıcı ve Ö. Güzel Akdemir, “Synthesis and potential antitumor activities of mandelic acid linked 2-aryl-1,3-thiazolidin-4-ones”, J. Res. Pharm., c. 26, sy. 4, ss. 931–940, 2025.
ISNAD Demir-yazıcı, Kübra - Güzel Akdemir, Özlen. “Synthesis and Potential Antitumor Activities of Mandelic Acid Linked 2-Aryl-1,3-Thiazolidin-4-Ones”. Journal of Research in Pharmacy 26/4 (Haziran 2025), 931-940.
JAMA Demir-yazıcı K, Güzel Akdemir Ö. Synthesis and potential antitumor activities of mandelic acid linked 2-aryl-1,3-thiazolidin-4-ones. J. Res. Pharm. 2025;26:931–940.
MLA Demir-yazıcı, Kübra ve Özlen Güzel Akdemir. “Synthesis and Potential Antitumor Activities of Mandelic Acid Linked 2-Aryl-1,3-Thiazolidin-4-Ones”. Journal of Research in Pharmacy, c. 26, sy. 4, 2025, ss. 931-40.
Vancouver Demir-yazıcı K, Güzel Akdemir Ö. Synthesis and potential antitumor activities of mandelic acid linked 2-aryl-1,3-thiazolidin-4-ones. J. Res. Pharm. 2025;26(4):931-40.