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 |
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| Institution: | 1. Faculty of Chemistry, Opole University, Opole 45-052, Poland;2. SHEE “Ukrainian State University of Chemical Technology”, 49007, Gagarina Avenue 8, Dnipropetrovsk, Ukraine;3. Zaporizhzhia State Medical University, 69035, Mayakovsky Avenue 26, Zaporozhye, Ukraine;1. Centre de Recherche Cerveau et Cognition, CNRS and Université Toulouse III – Paul Sabatier (UPS), 31052 Toulouse Cedex, France;1. Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute, Rochester Regional Health System, 1425 Portland Ave, Rochester, NY, United States;2. Legacy Pediatrics, Rochester, NY, United States |
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| Abstract: | Thirty three derivatives of 2-substituted 5,6,7,8-tetrahydrobenzo4,5]thieno2,3-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-phenethyl-5,6,7,8-tetrahydrobenzo4,5]thieno2,3-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 μg/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 μM and showed 25% cytotoxicity against RAW 264.7 cell line at 50 μg/mL. |
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| Keywords: | Tuberculosis Dormant tuberculosis |
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