Development of 1,3,4-Thiadiazole and Piperazine Fused Hybrid Quinazoline Derivatives as Dynamic Antimycobacterial Agents

Novel series of 1,3,4-thiadiazole and piperazine substituted quinazoline derivatives have been designed, synthesized, and tested in vitro for antimycobacterial activity. The synthetic procedure involved Suzuki C-C cross-coupling on a quinazoline ring and subsequently by the formation of 1,3,4-thiadiazole based piperazines. Many synthesized analogs were observed active against Mycobacterium H37Rv strain in preliminary analysis using the BACTEC MGIT method. A secondary antimycobacterial assay using the Lowenstein-Jensen MIC method indicates that bromo (7c), trifluoromethyl (7f), and hydroxy (7 h) groups substituted analogs have shown strong efficacy in the range of 3.12-6.25 mu g/mL. Active compounds were also tested for their cytotoxic activity against Human cervical (HeLa) cells at their MICs. The synthesized analogs were analyzed by IR, 1H NMR, 13 C NMR, MS, and elemental analysis for their structure determination.

Automated summary

1,3,4-thiadiazole and piperazine substituted quinazoline derivatives were synthesized and tested for their antimycobacterial activity in vitro. The bromo, trifluoromethyl, and hydroxy substituted analogs showed strong efficacy in the range of 3.12-6.25 μg/mL.