Anti-tubercular activities of 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine analogues endowed with high activity toward non-replicative Mycobacterium tuberculosis

作者：Samala Ganesh; Devi Parthiban Brindha; Saxena Shalini; Gunda Saritha; Yogeeswari Perumal; Sriram Dharmarajan^*

来源：Bioorganic & Medicinal Chemistry, 2016, 24(21): 5556-5564.

DOI：10.1016/j.bmc.2016.09.012

• Tuberculosis
• Dormant tuberculosis
• L-Alanine dehydrogenase
• Tetrahydrobenzo[4,5]thieno[2,3-d] pyrimidin-4-amine analogues

Thirty three derivatives of 2-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine analogues were synthesized by molecular modification of a reported antimycobacterial molecule (GSK163574A). Compounds were evaluated in vitro against actively replicative and nutrient starved non-replicative Mycobacterium tuberculosis (MTB), enzymatic screening and cytotoxicity against RAW 264.7 cell line. Among the compounds, 2-ethyl-N-phenethy1-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d] pyrimidin-4-amine (5c) was found to be the most active compound against non-replicative MTB with 2.7 log reduction of bacteria at 10 mu g/mL and was more potent than isoniazid (1.2 log reduction) and rifampicin (2.0 log reduction) at same dose level. Compound 5c also showed activity against MTB alanine dehydrogenase enzyme with IC50 of 1.82 +/- 0.42 mu M and showed 25% cytotoxicity against RAW 264.7 cell line at 50 mu g/mL.

• 出版日期2016-11-1