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

Abstract

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 µg/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.

Keywords:

• 1,3,4-Thiadiazole
• antimycobacterial activity
• piperazine
• quinazoline
• Suzuki coupling

Acknowledgements

The authors are thankful to the U.T. Administration of Dadra & Nagar Haveli and Daman & Diu, Veer Narmad South Gujarat University, Surat and the Principal, Government College, Daman for encouragement and facilities.

Disclosure statement

No potential conflict of interest was reported by the authors.