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

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.