Design and Synthesis of 1,3,4-Thiadiazole Derivatives as Novel Anticancer and Antitubercular Agents

Resumo

A series of novel 5-phenyl-substituted 1,3,4-thiadiazole-2-amines were designed, synthesized, and screened for their antitumor and antitubercular activities. The target compounds were synthesized starting from isocyanates and acid hydrazides by conventional and microwave-assisted protocols. The structures of the products were confirmed by ¹H NMR, ¹³C NMR, high-resolution mass spectrometry, and IR spectroscopy and elemental analysis. Some of the synthesized compounds showed significant invitro antitumor activities against breast cancer and normal human cell lines. Among them, N-benzyl-5-(4-fluorophenyl)-, N-benzyl-5-(4-nitrophenyl)-, and 5-phenyl-N-(p-tolyl)-1,3,4-thiadiazole-2-amines demonstrated higher inhibitory activities against the MDA-MB-231 cell line than the cisplatin control (IC₅₀ 3.3 ώM). N-Benzyl-5-(4-methoxyphenyl)-, 5-phenyl-N-[4-(trifluoromethyl)phenyl]methyl-, N-benzyl-5-(4-fluorophenyl)-, and N-benzyl-5-(4-nitrophenyl)-1,3,4-thiadiazole-2-amines exhibited high inhibitory activities against the HEK293T cell line (IC₅₀ 52.63, 42.67, 34.71, and 33.74 ώM, respectively), which were higher compared to the cisplatin control. In antitubercular activity testing against mycobacterium smegmatis MC155, 5-phenyl-N-[4-(trifluoromethyl)-phenyl]methyl-1,3,4-thiadiazole-2-amine proved to be a more potent agent (MIC 26.46 ώg/mL) compared to the Isoniazid control (12 ώg/mL). Potential bioactivities of the synthesized compounds were computed using Molinspiration and Molsoft software tools.