Polyfunctional Thiazole/Thiazolidinone Derivatives as a New Class of Heterocyclic Compounds with Novel Mechanisms of Anticancer Activity
DOI:
https://doi.org/10.15407/exp-oncology.2026.01.003Keywords:
thiazole, thiazolidinone, antitumor activity, biotargets, hybrid moleculesAbstract
Thiazole and thiazolidinone derivatives constitute an important class of heterocyclic compounds, widely investigated in modern medicinal chemistry for their diverse biological activities and significant potential for structural modification. Particular attention has focused on their anticancer properties and the design of multifunctional hybrid molecules with improved pharmacological profiles. This review summarizes recent advances in the synthesis and biological evaluation of functionally substituted condensed and non-condensed thiazole/thiazolidinone derivatives with anticancer activity. Available literature demonstrates that many of these compounds exhibit pronounced cytotoxic and pro-apoptotic effects across various tumor models. Their biological activity is associated with interactions with multiple molecular targets, including PPARγ receptors, integrins, PI3K/mtOR signaling pathways, histone deacetylases, matrix metalloproteina- ses, StAt3, and Pim-kinases. These multitarget mechanisms highlight the potential of these heterocyclic scaffolds for developing innovative anticancer agents. Analysis of structure–activity relationships has revealed promising directions for further optimization of the lead compounds. Overall, thiazole and thiazolidinone derivatives remain attractive plat- forms for the rational design of new anticancer drugs with improved selectivity and reduced toxicity.
References
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Жорстка практична альтернатива
Ось твій вичищений список. Я розліпив слова, відновив ініціали та імена, виправив медичні абревіатури (наприклад, TNF-α замість tNf-α, STAT3 замість StAt3) і склеїв DOI.
Golebiowski A, Klopfenstein SR, Portlock DE. Lead compounds discovered from libraries: part 2. Curr Opin Chem Biol. 2003;7(3):308-325. https://doi.org/10.1016/S1367-5931(03)00059-0
Carnero A. High throughput screening in drug discovery. Clin Transl Oncol. 2006;8:482-490. https://doi.org/10.1016/S1367-5931(03)00059-0
Dandapani S, Marcaurelle LA. Current strategies for diversity-oriented synthesis. Curr Opin Chem Biol. 2010;14(3):362-370. https://doi.org/10.1016/j.cbpa.2010.03.018
Rouf A, Tanyeli C. Bioactive thiazole and benzothiazole derivatives. Eur J Med Chem. 2015;97:911-927. https://doi.org/10.1016/j.ejmech.2014.10.058
Ayati A, Emami S, Asadipour A, et al. Recent applications of 1,3-thiazole core structure in the identification of new lead compounds and drug discovery. Eur J Med Chem. 2015;97:699-718. https://doi.org/10.1016/j.ejmech.2015.04.015
DrugBank Online [Internet]. DrugBank Data web service; 2023 [cited 2023]. Available from: https://go.drugbank.com/
Konechnyi Y, Lozynskyi A, Horishny V, et al. Synthesis of indoline-thiazolidinone hybrids with antibacterial and antifungal activities. Biopolym Cell. 2020;36(5):381-391. https://doi.org/10.7124/bc.000A3A
Lalloyer F, Staels B. Fibrates, glitazones, and peroxisome proliferator-activated receptors. Arterioscler Thromb Vasc Biol. 2010;30(5):894-899. https://doi.org/10.1161/ATVBAHA.108.179689
Bortolini M, Wright MB, Bopst M, et al. Examining the safety of PPAR agonists: current trends and future prospects. Expert Opin Drug Saf. 2013;12(1):65-79. https://doi.org/10.1517/14740338.2013.741585
Ahmadian M, Suh JM, Hah N, et al. PPARγ signaling and metabolism: the good, the bad and the future. Nat Med. 2013;19(5):557-566. https://doi.org/10.1038/nm.3159
Houseknecht KL, Cole BM, Steele PJ. Peroxisome proliferator-activated receptor gamma (PPARγ) and its ligands: a review. Domest Anim Endocrinol. 2002;22(1):1-23. https://doi.org/10.1016/S0739-7240(01)00117-5
Tachibana K, Yamasaki D, Ishimoto K. The role of PPARs in cancer. PPAR Res. 2008;2008:102737. https://doi.org/10.1155/2008/102737
Szychowski KA, Leja ML, Kaminskyy DV, et al. Anticancer properties of 4-thiazolidinone derivatives depend on peroxisome proliferator-activated receptor gamma (PPARγ). Eur J Med Chem. 2017;141:162-168. https://doi.org/10.1016/j.ejmech.2017.09.071
Sklyarova Y, Fomenko I, Lozynska I, et al. Hydrogen sulfide releasing 2-mercaptoacrylic acid-based derivative possesses cytoprotective activity in a small intestine of rats with medication-induced enteropathy. Sci Pharm. 2017;85(4):35. https://doi.org/10.3390/scipharm85040035
Inxight Drugs [Internet]. NCATS Inxight Drugs portal; 2023 [cited 2023]. Available from: https://drugs.ncats.io/
Ye X, Zhou W, Li Y, et al. Darbufelone, a novel anti-inflammatory drug, induces growth inhibition of lung cancer cells both in vitro and in vivo. Cancer Chemother Pharmacol. 2010;66:277-285. https://doi.org/10.1007/s00280-009-1161-z
Roszczenko P, Holota S, Szewczyk OK, et al. 4-Thiazolidinone-bearing hybrid molecules in anticancer drug design. Int J Mol Sci. 2022;23(21):13135. https://doi.org/10.3390/ijms232113135
Li M, Sala V, De Santis MC, et al. Phosphoinositide 3-kinase gamma inhibition protects from anthracycline cardiotoxicity and reduces tumor growth. Circulation. 2018;138(7):696-711. https://doi.org/10.1161/CIRCULATIONAHA.117.030352
Huang S, Liu Y, Chen Z, et al. PIK-75 overcomes venetoclax resistance via blocking PI3K-Akt signaling and MCL-1 expression in mantle cell lymphoma. Am J Cancer Res. 2022;12(3):1102-1115. PMCID:PMC8984906
Xie J, Li Q, Ding X, et al. GSK1059615 kills head and neck squamous cell carcinoma cells possibly via activating mitochondrial programmed necrosis pathway. Oncotarget. 2017;8(31):50814-50825. https://doi.org/10.18632/oncotarget.15135
Gong Y, Fan Z, Luo G, et al. The role of necroptosis in cancer biology and therapy. Mol Cancer. 2019;18(1):100. https://doi.org/10.1186/s12943-019-1029-8
Zheng W, Degterev A, Hsu E, et al. Structure–activity relationship study of a novel necroptosis inhibitor, necrostatin-7. Bioorg Med Chem Lett. 2008;18(18):4932-4935. https://doi.org/10.1016/j.bmcl.2008.08.058
Dayam R, Aiello F, Deng J, et al. Discovery of small molecule integrin αvβ3 antagonists as novel anticancer agents. J Med Chem. 2006;49(15):4526-4534. https://doi.org/10.1021/jm051296s
Hamidi H, Ivaska J. Every step of the way: integrins in cancer progression and metastasis. Nat Rev Cancer. 2018;18(9):533-548. https://doi.org/10.1038/s41568-018-0038-z
Bjorklund M, Aitio O, Stefanidakis M, et al. Stabilization of the activated αMβ2 integrin by a small molecule inhibits leukocyte migration and recruitment. Biochemistry. 2006;45(9):2862-2871. https://doi.org/10.1021/bi052238b
Suojanen J, Salo T, Sorsa T, et al. αMβ2 integrin modulator exerts antitumor activity in vivo. Anticancer Res. 2007;27(6B):3775-3781. PMID:18225532
Sawaguchi Y, Yamazaki R, Nishiyama Y, et al. Rational design of a potent pan-pim kinases inhibitor with a rhodanine–benzoimidazole structure. Anticancer Res. 2017;37(8):4051-4057. https://doi.org/10.21873/anticanres.11790
Vatolin S, Phillips JG, Jha BK, et al. Novel protein disulfide isomerase inhibitor with anticancer activity in multiple myeloma. Cancer Res. 2016;76(11):3340-3350. https://doi.org/10.1158/0008-5472.CAN-15-3099
Lee E. Emerging roles of protein disulfide isomerase in cancer. BMB Rep. 2017;50(8):401-410. https://doi.org/10.5483/bmbrep.2017.50.8.107
Huang MJ, Cheng YC, et al. A small-molecule c-Myc inhibitor, 10058-F4, induces cell-cycle arrest, apoptosis, and myeloid differentiation of human acute myeloid leukemia. Exp Hematol. 2006;34(11):1480-1489. https://doi.org/10.1016/j.exphem.2006.06.019
Miller DM, Thomas SD, Islam A, et al. c-Myc and cancer metabolism. Clin Cancer Res. 2012;18(20):5546-5553. https://doi.org/10.1158/1078-0432.CCR-12-0977
Degterev A, Lugovskoy A, Cardone M, et al. Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL. Nat Cell Biol. 2001;3(2):173-182. https://doi.org/10.1038/35055085
Reed JC, Miyashita T, Takayama S, et al. Bcl-2 family proteins: regulators of cell death involved in the pathogenesis of cancer and resistance to therapy. J Cell Biochem. 1996;60(1):23-32. https://doi.org/10.1002/(SICI)1097-4644(19960101)60:1<23::AID-JCB5>3.0.CO;2-5
Cutshall NS, O'Day C, Prezhdo M. Rhodanine derivatives as inhibitors of JSP-1. Bioorg Med Chem Lett. 2005;15(14):3374-3379. https://doi.org/10.1016/j.bmcl.2005.05.034
Shen Y, Luche R, Wei B, et al. Activation of the JNK signaling pathway by a dual-specificity phosphatase, JSP-1. Proc Natl Acad Sci U S A. 2001;98(24):13613-13618. https://doi.org/10.1073/pnas.231499098
Carter PH, Scherle PA, Muckelbauer JA, et al. Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF-α. Proc Natl Acad Sci U S A. 2001;98(21):11879-11884. https://doi.org/10.1073/pnas.211178398
Horiuchi T, Mitoma H, Harashima SI, et al. Transmembrane TNF-α: structure, function and interaction with anti-TNF agents. Rheumatology. 2010;49(7):1215-1228. https://doi.org/10.1093/rheumatology/keq031
Balkwill F. TNF-α in promotion and progression of cancer. Cancer Metastasis Rev. 2006;25:409-416. https://doi.org/10.1007/s10555-006-9005-3
Anh DT, Hai PT, Park EJ, et al. Exploration of certain 1,3-oxazole- and 1,3-thiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents. Bioorg Chem. 2020;101:103988. https://doi.org/10.1016/j.bioorg.2020.103988
Barneda-Zahonero B, Parra M. Histone deacetylases and cancer. Mol Oncol. 2012;6(6):579-589. https://doi.org/10.1016/j.molonc.2012.07.003
Ge L, Hu Q, Shi M, et al. Design and discovery of novel thiazole derivatives as potential MMP inhibitors to protect against acute lung injury in sepsis rats via attenuation of inflammation and apoptotic oxidative stress. RSC Adv. 2017;7(52):32909-32922. https://doi.org/10.1039/C7RA03511J
Shay G, Lynch CC, Fingleton B. Moving targets: emerging roles for MMPs in cancer progression and metastasis. Matrix Biol. 2015;44:200-206. https://doi.org/10.1016/j.matbio.2015.01.019
Hu CM, Zhu J, Guo XE, et al. Novel small molecules disrupting Hec1/Nek2 interaction ablate tumor progression by triggering Nek2 degradation through a death-trap mechanism. Oncogene. 2015;34(10):1220-1230. https://doi.org/10.1038/onc.2014.67
Wilson KJ, Illig CR, Subasinghe N, et al. Synthesis of thiophene-2-carboxamidines containing 2-amino-thiazoles and their biological evaluation as urokinase inhibitors. Bioorg Med Chem Lett. 2001;11(7):915-918. https://doi.org/10.1016/S0960-894X(01)00102-0
Shen X, Zhao L, Chen P, et al. A thiazole-derived oridonin analogue exhibits antitumor activity by directly and allosterically inhibiting STAT3. J Biol Chem. 2019;294(46):17471-17486. https://doi.org/10.1074/jbc.RA119.009801
Aly AA, Brase S, Hassan AA, et al. Design, synthesis, and molecular docking of paracyclophanyl-thiazole hybrids as novel CDK1 inhibitors and apoptosis-inducing anti-melanoma agents. Molecules. 2020;25(23):5569. https://doi.org/10.3390/molecules25235569
Xie XX, Li H, Wang J, et al. Synthesis and anticancer effects evaluation of 1-alkyl-3-(6-(2-methoxy-3-sulfonylamino-pyridin-5-yl)benzo[d]thiazol-2-yl)urea as anticancer agents with low toxicity. Bioorg Med Chem. 2015;23(19):6477-6485. https://doi.org/10.1016/j.bmc.2015.08.013
Luke RW, Ballard P, Buttar D, et al. Novel thienopyrimidine and thiazolopyrimidine kinase inhibitors with activity against Tie-2 in vitro and in vivo. Bioorg Med Chem Lett. 2009;19(23):6670-6674. https://doi.org/10.1016/j.bmcl.2009.10.001
Duran CL, Borriello L, Karagiannis GS, et al. Targeting Tie2 in the tumor microenvironment: from angiogenesis to dissemination. Cancers. 2021;13(22):5730. https://doi.org/10.3390/cancers13225730
Al-Rashood ST, Elshahawy SS, El-Qaias AM, et al. New thiazolopyrimidine as anticancer agents: synthesis, biological evaluation, DNA binding, molecular modeling and ADMET study. Bioorg Med Chem Lett. 2020;30(23):127611. https://doi.org/10.1016/j.bmcl.2020.127611
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