Abstract
Cancer is known as one of the main causes of death in the world; and many compounds have been synthesized to date with potential use in cancer therapy. Thiazole is a versatile heterocycle, found in the structure of many drugs in use as well as anticancer agents. This review provides an overview of recent advances in thiazole-bearing compounds as anticancer agents with particular emphasis on their mechanism of action in cancerous cells. Chemical designs, structure–activity relationships and relevant preclinical properties have been comprehensively described.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1. Cancer survivorship: an integral part of Europe's research agenda. Mol. Oncol. 13(3), 624–635 (2018).
- 2. Synthesis and evaluation of thiazolidinone–pyrazole conjugates as anticancer and antimicrobial agents. Future Med. Chem. 10(9), 1017–1036 (2018).
- 3. . Overcoming ABC transporter-mediated multidrug resistance: the dual role of tyrosine kinase inhibitors as multitargeting agents. Eur. J. Med. Chem. 142, 271–289 (2017).
- 4. . Nanoparticles in cancer treatment: opportunities and obstacles. Curr. Drug Targets 19(1), 1696–1709 (2018).
- 5. . Cell-cycle dysregulation and anticancer therapy. Trends Pharmacol. Sci. 24(3), 139–145 (2003).
- 6. Synthesis and anticancer evaluation effects of 1-alkyl-3-(6-(2-methoxy-3-sulfonylaminopyridin-5-yl) benzo[d] thiazol-2-yl) urea as anticancer agents with low toxicity. Bioorg. Med. Chem. 23(19), 6477–6485 (2015).
- 7. . Recent applications of 1,3-thiazole core structure in the identification of new lead compounds and drug discovery. Eur. J. Med. Chem. 97, 699–718 (2015). •• Highlights the importance of thiazole core in the new lead generation.
- 8. In vitro antioxidant activity of thiazolidinone derivatives of 1,3-thiazole and 1,3,4-thiadiazole. Chem. Biol. Interact. 286, 119–131 (2018).
- 9. . Synthesis of 4-benzyl-1,3-thiazole derivatives as potential anti-inflammatory agents: an analogue-based drug design approach. J. Enzyme Inhib. Med. Chem. 24(3), 890–897 (2009).
- 10. . Synthesis of some new 2-(3-pyridyl)-4,5-disubstituted thiazoles as potent antimicrobial agents. Eur. J. Med. Chem. 62, 270–279 (2013).
- 11. Synthesis, molecular modeling studies and evaluation of antifungal activity of a novel series of thiazole derivatives. Eur. J. Med. Chem. 151, 248–260 (2018).
- 12. New thiazolyl-coumarin hybrids: design, synthesis, characterization, x-ray crystal structure, antibacterial and antiviral evaluation. J. Mol. Struct. 1166, 147–154 (2018).
- 13. . 1‐[(2‐arylthiazol‐4‐yl) methyl] azoles as a new class of anticonvulsants: design, synthesis, in vivo screening, and in silico drug‐like properties. Chem. Biol. Drug Des. 78(5), 844–852 (2011).
- 14. . Thiazole: a promising heterocycle for the development of potent CNS active agents. Eur. J. Med. Chem. 92, 1–34 (2015).
- 15. . Novel thiazole derivatives: a patent review (2008–2012, Part 1). Expert Opin. Ther. Patents 24(2), 201–216 (2014). • Comprehensive review on thiazole derivatives.
- 16. Clinical pharmacokinetics and pharmacodynamics of dabrafenib. Clin. Pharmacokinet. 58(4), 451–467 (2019).
- 17. . Dasatinib: a review in chronic myeloid leukaemia and Ph+ acute lymphoblastic leukaemia. Drugs 77(1), 85–96 (2017).
- 18. . Understanding microtubule dynamics for improved cancer therapy. Cell Mol. Life Sci. 62(24), 3039–3056 (2005). •• Highlights the importance of our knowledge about microtubule dynamics and cancer therapy.
- 19. . Anti‐mitotic activity of colchicine and the structural basis for its interaction with tubulin. Med. Res. Rev. 28(1), 155–183 (2008).
- 20. . Recent advances of cytotoxic chalconoids targeting tubulin polymerization: synthesis and biological activity. Eur. J. Med. Chem. 121, 610–639 (2016).
- 21. . An overview of tubulin inhibitors that interact with the colchicine binding site. Pharm. Res. 29(11), 2943–2971 (2012). •• Comprehensive review of tubulin polymerization inhibitors.
- 22. . Antimitotic natural products combretastatin A-4 and combretastatin A-2: studies on the mechanism of their inhibition of the binding of colchicine to tubulin. Biochemistry 28(17), 6984–6991 (1989).
- 23. Combretastatin A-4 analogs as anticancer agents. Mini Rev. Med. Chem. 7(12), 1186–1205 (2007).
- 24. . [4-(imidazol-1-yl)thiazol-2-yl]phenylamines. A novel class of highly potent colchicine site binding tubulin inhibitors: synthesis and cytotoxic activity on selected human cancer cell lines. J. Med. Chem. 49(19), 5769–5776 (2006).
- 25. 2-arylamino-4-amino-5-aroylthiazoles. “One-pot” synthesis and biological evaluation of a new class of inhibitors of tubulin polymerization. J. Med. Chem. 52(17), 5551–5555 (2009).
- 26. One-pot synthesis and biological evaluation of 2-pyrrolidinyl-4-amino-5-(3′, 4′, 5′-trimethoxybenzoyl) thiazole: a unique, highly active antimicrotubule agent. Eur. J. Med. Chem. 46(12), 6015–6024 (2011).
- 27. Discovery and optimization of a series of 2-aryl-4-amino-5-(3′, 4′, 5′-trimethoxybenzoyl) thiazoles as novel anticancer agents. J. Med. Chem. 55(11), 5433–5445 (2012).
- 28. Convergent synthesis and biological evaluation of 2-amino-4-(3′, 4′, 5′-trimethoxyphenyl)-5-aryl thiazoles as microtubule targeting agents. J. Med. Chem. 54(14), 5144–5153 (2011).
- 29. Synthesis and biological evaluation of 2-substituted-4-(3′, 4′, 5′-trimethoxy phenyl)-5-aryl thiazoles as anticancer agents. Bioorg. Med. Chem. 20(24), 7083–7094 (2012).
- 30. Synthesis and biological evaluation of 3-(trimethoxyphenyl)-2 (3H)-thiazole thiones as combretastatin analogs. Eur. J. Med. Chem. 70, 692–702 (2013).
- 31. Argyrins, immunosuppressive cyclic peptides from myxobacteria. I. Production, isolation, physico-chemical and biological properties. J. Antibiot. 55(6), 543–551 (2002).
- 32. Synthesis and superpotent anticancer activity of tubulysins carrying non-hydrolysable N-substituents on tubuvaline. Chemistry 23(24), 5842–5850 (2017).
- 33. . Apoptosis: a link between cancer genetics and chemotherapy. Cell 108(2), 153–164 (2002).
- 34. . Apoptosis: an introduction for the endodontist. Int. Endod. J. 36(4), 237–245 (2003).
- 35. . Regulators of apoptosis as anticancer targets. Hematol. Oncol. Clin. North Am. 16(5), 1255–1267 (2002).
- 36. . The roles of therapy-induced autophagy and necrosis in cancer treatment. Clin. Cancer Res. 13(24), 7271–7279 (2007).
- 37. . Apoptosis and non-apoptotic deaths in cancer development and treatment response. Cancer Treat. Rev. 34(8), 737–749 (2008). •• Highlights the role of apoptosis in cancer development and cancer therapy.
- 38. . 2-(3-indolyl)-N-arylthiazole-4-carboxamides: synthesis and evaluation of antibacterial and anticancer activities. Bioorg. Med. Chem. Lett. 25(19), 4225–4231 (2015).
- 39. . Molecular hybridization of bioactives: synthesis and antitubercular evaluation of novel dibenzofuran embodied homoisoflavonoids via Baylis–Hillman reaction. Bioorg. Med. Chem. Lett. 22(24), 7426–7430 (2012).
- 40. . Synthesis and antitumor activity of novel N-(5-benzyl-4-(tert-butyl)thiazol-2-yl)-2-(piperazin-1-yl)acetamides. Res. Chem. Intermed. 43(8), 4833–4850 (2017).
- 41. . Synthesis, anticancer activity and mechanism of action of new thiazole derivatives. Eur. J. Med. Chem. 144, 874–886 (2018).
- 42. Anti-liver cancer activity in vitro and in vivo induced by 2-pyridyl 2,3-thiazole derivatives. Toxicol. Appl. Pharmacol. 329, 212–223 (2017).
- 43. Antitumor and immunomodulatory activities of thiosemicarbazones and 1,3-thiazoles in Jurkat and HT-29 cells. Biomed. Pharmacother. 82, 555–560 (2016).
- 44. Synthesis, antitumor activity and mechanism of action of novel 1,3-thiazole derivatives containing hydrazide – hydrazone and carboxamide moiety. Bioorg. Med. Chem. Lett. 26(14), 3263–3270 (2016).
- 45. Synthesis and biological evaluation of 4-amino-5-cinnamoylthiazoles as chalcone-like anticancer agents. Eur. J. Med. Chem. 145, 404–412 (2018).
- 46. Synthesis and biological evaluation of new coumarins bearing 2,4-diaminothiazole-5-carbonyl moiety. Eur. J. Med. Chem. 155, 483–491 (2018).
- 47. Synthesis and function of 3-phosphorylated inositol lipids. Annu. Rev. Biochem. 70, 535–602 (2001).
- 48. Synthesis and biological evaluation of imidazo [1,2-a] pyridine derivatives as novel PI3 kinase p110α inhibitors. Bioorg. Med. Chem. 15(1), 403–412 (2007).
- 49. Development of isoform selective PI3-kinase inhibitors as pharmacological tools for elucidating the PI3K pathway. Bioorg. Med. Chem. Lett. 22(17), 5445–5450 (2012). •• Described progress toward isoform selective phosphatidylinositol-3-kinase inhibitors using an automated parallel synthesis strategy.
- 50. Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. Bioorg. Med. Chem. Lett. 23(13), 3741–3748 (2013).
- 51. Identification and optimisation of a 4′,5-bisthiazole series of selective phosphatidylinositol-3 kinase alpha inhibitors. Bioorg. Med. Chem. Lett. 25(17), 3569–3574 (2015).
- 52. Identification and optimisation of 4,5-dihydrobenzo series of selective phosphatidylinositol-3 kinase alpha inhibitors. Bioorg. Med. Chem. Lett. 25(17), 3575–3581 (2015).
- 53. . Discovery and optimization of a series of 2-aminothiazole-oxazoles as potent phosphoinositide 3-kinase c inhibitors. Bioorg. Med. Chem. Lett. 22(24), 7534–7538 (2012).
- 54. . (TASP0415914) as an orally potent phosphoinositide 3-kinase c inhibitor for the treatment of inflammatory diseases. Bioorg. Med. Chem. 21(24), 7578–7583 (2013).
- 55. Preparation and optimization of new 4-(2-(indolin-1-yl)-2-oxoethyl)-2-morpholinothiazole-5-carboxylic acid and amide derivatives as potent and selective PI3Kβ inhibitors. Bioorg. Med. Chem. Lett. 24(6), 1506–1510 (2014).
- 56. Indeno [1,2-b] indole derivatives as a novel class of potent human protein kinase CK2 inhibitors. Bioorg. Med. Chem. 20(7), 2282–2289 (2012).
- 57. . Three cyclin-dependent kinases preferentially phosphorylate different parts of the C-terminal domain of the large subunit of RNA polymerase II. Eur. J. Biochem. 271(5), 1004–1014 (2004).
- 58. . Protein kinase CK2 in human diseases. Curr. Med. Chem. 15(19), 1870–1886 (2008). • Contains considerable information on the potential roles of CK2 in various diseases including cancer.
- 59. Discovery of aminothiazole inhibitors of cyclin-dependent kinase 2: synthesis, x-ray crystallographic analysis, and biological activities. J. Med. Chem. 45(18), 3905–3927 (2002).
- 60. N-(cycloalkylamino)acyl-2-aminothiazole Inhibitors of cyclin-dependent kinase piperidinecarboxamide (BMS-387032), a highly efficacious and selective antitumor agent. J. Med. Chem. 47(7), 1719–1728 (2004).
- 61. A diaminocyclohexyl analog of SNS-032 with improved permeability and bioavailability properties. Bioorg. Med. Chem. Lett. 18(21), 5763–5765 (2008).
- 62. Synthesis and biological activity of N-aryl-2-aminothiazoles: potent pan inhibitors of cyclin-dependent kinases. Bioorg. Med. Chem. Lett. 14(11), 2973–2977 (2004).
- 63. Discovery of a novel family of CDK Inhibitors with the program LIDAEUS: structural basis for ligand-induced disordering of the activation loop. Structure 11(3), 399–410 (2003).
- 64. 2-anilino-4-(thiazol-5-yl) pyrimidine CDK inhibitors: synthesis, SAR analysis, x-ray crystallography, and biological activity. J. Med. Chem. 47(7), 1662–1675 (2004).
- 65. Design, synthesis, and evaluation of 2-methyl- and 2-amino- N-aryl-4,5-dihydrothiazolo-[4,5-h] quinazolin-8-amines as ring-constrained 2-anilino-4-(thiazol-5-yl) pyrimidine cyclin-dependent kinase inhibitors. J. Med. Chem. 53(4), 2136–2145 (2010).
- 66. Synthesis, structure-activity relationship and biological evaluation of 2,4,5-trisubstituted pyrimidine CDK inhibitors as potential anti-tumour agents. Eur. J. Med. Chem. 70, 447–455 (2013).
- 67. Development of highly potent and selective diaminothiazole inhibitors of cyclin-dependent kinases. J. Med. Chem. 56(10), 3768–3782 (2013). • Interesting article in the field of thiazole inhibitors of cyclin-dependent kinases.
- 68. Design, synthesis and biological evaluation of thiazolidinone derivatives as potential EGFR and HER-2 kinase inhibitors. Bioorg. Med. Chem. 18(1), 314–319 (2010).
- 69. . Autocrine VEGF signaling synergizes with EGFR in tumor cells to promote epithelial cancer development. Cell 140(2), 268–279 (2010).
- 70. . Synthesis, molecular modeling, and biological evaluation of cinnamic acid metronidazole ester derivatives as novel anticancer agents. Bioorg. Med. Chem. 18(14), 4991–4966 (2010).
- 71. . Convergent approach for commercial synthesis of gefitinib and erlotinib. Org. Process Res. Dev. 11(5), 813–816 (2007).
- 72. . Synthesis, molecular docking and evaluation of thiazolyl-pyrazoline derivatives as EGFR TK inhibitors and potential anticancer agents. Bioorg. Med. Chem. Lett. 21(18), 5374–5377 (2011).
- 73. Synthesis and biological evaluation of compounds which contain pyrazole, thiazole and naphthalene ring as antitumor agents. Bioorg. Med. Chem. Lett. 24(10), 2324–2328 (2014).
- 74. . Synthesis, molecular modeling studies and biological evaluation of novel pyrazole derivatives as antitumor and EGFR inhibitors. IJPT 8(4), 25192–25209 (2016).
- 75. . Autocrine functions of VEGF in breast tumor cells: adhesion, survival, migration and invasion. Cell Adh. Migr. 6(6), 547–553 (2012). •• Contains considerable information about functions of VEGF.
- 76. . Role of VEGF/VEGFR in the pathogenesis of leukemias and as treatment targets. Oncol. Rep. 28(6), 1935–1944 (2012).
- 77. The discovery of N-(1,3-thiazol-2-yl) pyridin-2-amines as potent inhibitors of KDR kinase. Bioorg. Med. Chem. Lett. 14(11), 2941–2945 (2004). • Design of new lead compounds as selective kinase domain region kinase inhibitors.
- 78. Potent N-(1,3-thiazol-2-yl)pyridin-2-amine vascular endothelial growth factor receptor tyrosine kinase inhibitors with excellent pharmacokinetics and low affinity for the hERG ion channel. J. Med. Chem. 47(25), 6363–6372 (2004).
- 79. Potent 2-[(pyrimidin-4-yl)amine}-1,3-thiazole-5-carbonitrile-based inhibitors of VEGFR-2 (KDR) kinase. Bioorg. Med. Chem. Lett. 16(5), 1146–1150 (2006).
- 80. . N-(aryl)-4-(azolylethyl)thiazole-5-carboxamides: novel potent inhibitors of VEGF receptors I and II. Bioorg. Med. Chem. Lett. 16(3), 602–606 (2006).
- 81. SAR of a novel “anthranilamide like” series of VEGFR-2, multi protein kinase inhibitors for the treatment of cancer. Bioorg. Med. Chem. Lett. 17(15), 4378–4381 (2007).
- 82. . 1-piperazinylphthalazines as potential VEGFR-2 inhibitors and anticancer agents: synthesis and in vitro biological evaluation. Eur. J. Med. Chem. 107, 165–179 (2016).
- 83. . Synthesis of piperazine-based thiazolidinones as VEGFR2 tyrosine kinase inhibitors inducing apoptosis. Future Med. Chem. 9(15), 1709–1729 (2017).
- 84. . Metastasis: from dissemination to organ-specific colonization. Nat. Rev. Cancer. 9(4), 274–284 (2009).
- 85. LIM kinases are required for invasive path generation by tumor and tumor-associated stromal cells. J. Cell Biol. 191(1), 169–185 (2010).
- 86. Modulation of cofilin phosphorylation by inhibition of the Lim family kinases. Bioorg. Med. Chem. Lett. 22(18), 5995–5998 (2012).
- 87. Discovery, development and SAR of aminothiazoles as LIMK inhibitors with cellular anti-invasive properties. J. Med. Chem. 58(20), 8309–8313 (2015). •• Interesting article about discovery of aminothiazoles as LIMK inhibitors.
- 88. . p53 ubiquitination: Mdm2 and beyond. Mol. Cell. 21(3), 307–315 (2006).
- 89. . Discovery of specific inhibitors of human USP7/HAUSP deubiquitinating enzyme. Chem. Biol. 19(4), 467–477 (2012).
- 90. A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in multiple myeloma cells and overcomes bortezomib resistance. Cancer Cell. 22(3), 345–358 (2013).
- 91. Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes. Chem. Biol. 18(11), 1401–1412 (2011).
- 92. Synthesis and biological evaluation of thiazole derivatives as novel USP7 inhibitors. Bioorg. Med. Chem. Lett. 27(4), 845–849 (2017).
- 93. Novel inhibitors of the MDM2-p53 interaction featuring hydrogen bond acceptors as carboxylic acid isosteres. J. Med. Chem. 57(7), 2963–2988 (2014).
- 94. Small molecule RITA binds to p53, blocks p53–HDM-2 interaction and activates p53 function in tumors. Nat. Med. 10(12), 1321–1328 (2004).
- 95. . Correction ablation of key oncogenic pathways by RITA-reactivated p53 is required for efficient apoptosis. Cancer Cell. 31(5), 724–726 (2017).
- 96. CRISPR-Cas9-based target validation for p53-reactivating model compounds. Nat. Chem. Biol. 12(1), 22–28 (2016).
- 97. . RITA mimics: synthesis and mechanistic evaluation of asymmetric linked trithiazoles. ACS Med. Chem. Lett. 8(4), 401–406 (2017).
- 98. Synthesis and biological evaluation of 2-phenylthiazole-4-carboxamide derivatives as anticancer agents. Eur. J. Med. Chem. 45, 5384–5389 (2010).
- 99. Thiazolyl N-benzyl-substituted acetamide derivatives: synthesis, SRC kinase inhibitory and anticancer activities. Eur. J. Med. Chem. 46, 4853–4858 (2011).
- 100. . AAA ATPase p97/VCP: cellular functions, disease and therapeutic potential role of VCP in inflammatory signalling and ER stress. J. Cell Mol. Med. 12(6), 2511–2518 (2008).
- 101. 2-anilino-4-aryl-1,3-thiazole inhibitors of valosin-containing protein (VCP or p97). Bioorg. Med. Chem. Lett. 20(5), 1677–1679 (2010).
- 102. Efficacy of biological agents in metastatic triple-negative breast cancer. Cancer Treat. Rev. 40(5), 605–613 (2014).
- 103. Design and optimization of hybrid of 2,4-diaminopyrimidine and arylthiazole scaffold as anticancer cell proliferation and migration agents. Eur. J. Med. Chem. 96, 269–280 (2015).