1,3,4-Oxadiazole N -Mannich Bases: Synthesis, Antimicrobial, and Anti-Proliferative Activities

The reaction of 5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3 )-thione with formaldehyde solution and primary aromatic amines or 1-substituted piperazines, in ethanol at room temperature yielded the corresponding -Mannich bases 3-arylaminomethyl-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3 )-thiones - or 3-[(4-substituted piperazin-1-yl)methyl]-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3 )-thiones - , respectively. The in vitro inhibitory activity of compounds - and - was assessed against pathogenic Gram-positive, Gram-negative bacteria, and the yeast-like pathogenic fungus . The piperazinomethyl derivatives and displayed broad-spectrum antibacterial activities the minimal inhibitory concentration (MIC) 0.5-8 μg/mL) and compounds , , and showed potent activity against the tested Gram-positive bacteria. In addition, the anti-proliferative activity of the compounds was evaluated against prostate cancer (PC3), human colorectal cancer (HCT-116), human hepatocellular carcinoma (HePG-2), human epithelioid carcinoma (HeLa), and human breast cancer (MCF7) cell lines. The optimum anti-proliferative activity was attained by compounds , , and .