Document Type : Original Paper
Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Islamic Republic of Iran
Cancer has been become threatening the health and life of humans. Therefore, attempt to discovery more effective anticancer agents continue. Thiadiazole derivatives have been shown remarkable effects among chemotherapeutic agents. In this study, hybrid molecules containing thiadiazole amide derivatives -aromatic amines (anthranilic acid and 2, 5 dichloro aniline) were synthesized in multi-step reactions including N-amidation and S-alkylation of thiadiazole. Synthesized compounds were assayed by MTT test against three cell lines. Molecular docking was performed on Src tyrosine kinases. Compounds 5a, 5b and 8 rendered remarkable cytotoxic properties on HeLa with IC50‹ 60 µM. Compound 5b showed significant cytotoxic effect on both cancer cell lines compared to other tested derivatives. Compound 5a with ΔG = -8.05kcal/mol was the best compound among docked compounds.The results revealed that the quiddity of the amide substitution has a definitive role in the cytotoxic activity.
- Zhang K, Wang P, Xuan LN, Fu XY, Jing F, Li S, Liu YM, Chen BQ. Synthesis and antitumor activities of novel hybrid molecules containing 1, 3, 4-oxadiazole and 1, 3, 4-thiadiazole bearing Schiff base moiety. Bioorg & Med ChemLett. 2014; 24 (22):5154-6.
- Taher AT, Georgey HH, El-Subbagh HI. Novel 1, 3, 4-heterodiazole analogues: synthesis and in-vitro antitumor activity. Eur J Med Chem. 2012, 47:445-51.
- Aliabadi A, Fereidooni R, Kiani A. Synthesis and Cytotoxicity Evaluation of N-(5-(Substituted-benzylthio)-1, 3, 4-thiadiazole-2-yl)-2-p-nitrophenylacetamide Derivatives as Potential Anticancer Agents. Iran.J Chem Chem Eng). 2019; 38(1):49-55.
- Aliabadi A, Eghbalian E, Kiani A. Synthesis and evaluation of the cytotoxicity of a series of 1, 3, 4-thiadiazole based compounds as anticancer agents. IranJ Basic Med Sci. 2013; 16(11):1133.
- Yang XH, Wen Q, Zhao TT, Sun J, Li X, Xing M, Lu X, Zhu HL. Synthesis, biological evaluation, and molecular docking studies of cinnamic acyl 1, 3, 4-thiadiazole amide derivatives as novel antitubulin agents. Bioorg & Med Chem. 2012; 20(3):1181-7.
- Kaur H, Kaur H, Chawla A, Baghel U.S, Dhawan R.K. Thiadiazole: An amazing anticancer moiety. IntJ Pharm Chem. 2014; 04 (01):1-5.
- Hassanzadeh F, Jafari E, Shojaei F, Sadeghi-Aliabadi H. Synthesis and cytotoxic activity evaluation of some new 1, 3, 4-oxadiazole, 1, 3, 4-thiadiazole and 1, 2, 4-triazole derivatives attached to phthalimide. Res Pharm Sci. 2021; 16(6):634.
- Hassanzadeh F, Jafari E, Zarabi M, Khodarahmi G, Vaseghi G. Synthesis, cytotoxic evaluation, and molecular docking studies of some new 1, 3, 4-oxadiazole-based compounds. Res Pharm Sci. 2020; 15(5):454.
- Hassanzadeh F, Sadeghi-Aliabadi H, Jafari E, Sharifzadeh A, Dana N. Synthesis and cytotoxic evaluation of some quinazolinone-5-(4-chlorophenyl) 1, 3, 4-oxadiazole conjugates. Res Pharm Sci. 2019;14(5):408.
- Hassanzadeh F, Sadeghi-Aliabadi H, Nikooei S, Jafari E, Vaseghi G. Synthesis and cytotoxic evaluation of some derivatives of triazole-quinazolinone hybrids. Res .PharmSci 2019; 14(2):130.
- Jain AK, Sharma S, Vaidya A, Ravichandran V, Agrawal RK. 1, 3, 4‐Thiadiazole and its derivatives: A review on recent progress in biological activities. Chem Biol Drug Des. 2013; 81(5):557-76.
- Parmar KC, Umrigar NH. Review article on synthesis of 1, 3, 4-thiadiazole derivatives and it’s biological activity. J Chem Pharm Res. 2017;9(6):202-14.
- Khalilullah HA, Khan MU, Mahmood DA, Akhtar JA, Osman GA. 1, 3, 4-Thiadiazole: a biologically active scaffold. Int. J Pharm Pharm Sci. 2014; 6(9):8-15.
- Rezaei, Z; Moghimi, S; Javaheri, R; Asadi, Mi; Mahdavi, M; Shabani, S; Edraki, N; Firuzi, O; Safavi, M; Amini, M; Asadipour, A; Zeinalzadeh E; Firoozpour, L; Foroumadi, A Synthesis and Biological Evaluation of 1,3,4-Thiadiazole Linked Phthalimide Derivatives as Anticancer Agents. Lett Drug Des Discov 2017; 10 (14): 1138-1144
- Sun J, Yang YS, Li W, Zhang YB, Wang XL, Tang JF, Zhu HL. Synthesis, biological evaluation and molecular docking studies of 1, 3, 4-thiadiazole derivatives containing 1, 4-benzodioxan as potential antitumor agents. Bioorg & Med Chem Lett ; 2011 21(20):6116-21.
- Radi M, Crespan E, Botta G, Falchi F, Maga G, Manetti F, Corradi V, Mancini M, Santucci MA, Schenone S, Botta M. Discovery and SAR of 1, 3, 4-thiadiazole derivatives as potent Abl tyrosine kinase inhibitors and cytodifferentiating agents. Bioorg & Med. Chem Lett ; 2008 18(3):1207-11.
- Zhao L, Li X, Zhang L, Ye T, Zhu Y, Wei Y, Yang S, Yu L. Novel small molecules as apoptosis inducers: Synthesis, preliminary structure–activity relationships, and in vitro biological evaluation. Bioorg & Med Chem Lett. 2013; 23(8):2293-7.
- Chakravorty S, Kleina HF, Hodson LE, Rabillier M, Fang Z, Richters A, Pelly SC, Rauh D, Van Otterlo WA. Synthesis of novel piperazine-linked anthranilic acids as potential small molecule kinase inhibitors. S Afr J Chem .2014; 67:71-9.
- Doungsoongnuen S, Worachartcheewan A, Pingaew R, Suksrichavalit T, Prachayasittikul S, Ruchirawat S, Prachayasittikul V. Investigation on biological activities of anthranilic acid sulfonamide analogs. EXCLI J. 2011; 10:155.
- Hassanzadeh F, Jafari E, Hakimelahi GH, Khajouei MR, Jalali M, Khodarahmi GA. Antibacterial, antifungal and cytotoxic evaluation of some new quinazolinone derivatives. Res Pharm Sci 2012; 7(2):87.
- Shi L, Hu R, Wei Y, Liang Y, Yang Z, Ke S. Anthranilic acid-based diamides derivatives incorporating aryl-isoxazoline pharmacophore as potential anticancer agents: Design, synthesis and biological evaluation. Eur J Med Chem. 2012; 54: 549-556.
- Jafari E, Khodarahmi G, Hassanzadeh F, Hakimelahi G, Tsai F. Synthesis of some new tricyclic 4 (3H)-quinazolinone derivatives. Res Pharm Sci. 2012; 7(5):606.
- Hassanzadeh F, Khajouei MR, Hakimelahi GH, Jafari E, Khodarahmi GA. Synthesis of some new 2, 3-disubstituted-4 (3H) quinazolinone derivatives. Res Pharm Sci 2012;7(1):23.
- Xie C, Tang LM, Li FN, Guan LP, Pan CY, Wang SH. Structure-based design, synthesis, and anticonvulsant activity of isatin-1-N-phenylacetamide derivatives. Med Chem. Res. 2014;23(5):2161-8.
- Hassanzadeh F, Jafari E, Zarei S, Sadeghi-aliabadi H. Synthesis, Cytotoxic Effect Assessment and Molecular Docking Studies of Disubstituted Thiadiazole Including Oxadiazole as Hybrid Component. Hacet Univ J Fac. 2022; 42(4):228-37.
- Mohammadi-Farani A, Bahrami T, Aliabadi A. Synthesis, docking and cytotoxicity evaluation of N-(5-(benzyl-thio)-1, 3, 4-thiadiazol-2-yl)-2-(3-methoxyphenyl) acetamide derivatives as tyrosine kinase inhibitors with potential anticancer activity. J Rep PharmSci. 2014; 3(2):159.