Dehydrozingerone Inspired Styryl Hydrazine Thiazole Hybrids as Promising Class of Antimycobacterial Agents

作者：Hampannavar Girish A; Karpoormath Rajshekhar^*; Palkar Mahesh B; Shaikh Mahamadhanif S; Chandrasekaran Balakumar

来源：ACS Medicinal Chemistry Letters, 2016, 7(7): 686-691.

DOI：10.1021/acsmedchemlett.6b00088

• Antimycobacterial activity
• bactericidal
• dehydrozingerone
• NIAID
• thiazole

Series of styryl hydrazine thiazole hybrids inspired from dehydrozingerone (DZG) scaffold were designed and synthesized by molecular hybridization approach. In vitro antimycobacterial activity of synthesized compounds was evaluated against Mycobacterium tuberculosis H(37)Rv strain. Among the series, compound 6o exhibited significant activity (MIC = 1.5 mu M; IC50 = 0.48 mu M) along with bactericidal (MBC = 12 mu M) and intracellular antimycobacterial activities (IC50 = <0.098 mu M). Furthermore, 6o displayed prominent antimycobacterial activity under hypoxic (MIC = 46 mu M) and normal oxygen (MIC = 0.28 mu M) conditions along with antimycobacterial efficiency against isoniazid (MIC = 3.2 mu M for INH-R1; 1.5 mu M for INH-R2) and rifampicin (MIC = 2.2 mu M for RIF-R1; 6.3 mu M for RIF-R2) resistant strains of Mtb. Presence of electron donating groups on the phenyl ring of thiazole moiety had positive correlation for biological activity, suggesting the importance of molecular hybridization approach for the development of newer DZG clubbed hydrazine thiazole hybrids as potential antimycobacterial agents.

• 出版日期2016-7