Pharmacophore mapping,molecular docking,chemical synthesis of some novel pyrrolyl benzamide derivatives and evaluation of their inhibitory activity against enoyl-ACP reductase (InhA) and Mycobacterium tuberculosis |
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| Affiliation: | 1. Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T’s College of Pharmacy, Sangolli Rayanna Nagar, Dharwad, Karnataka, India;2. Department of PG Studies and Research in Chemistry, Vijayanagar College, Hosapete, Karnataka, India;3. Universite de Toulouse, UPS, Laboratoire de Synthese et Physico-chimie de Molecules d’Interet Biologique, LSPCMIB, 118 Roote de Narbonne, F-31062 Toulouse Cedex 9, France;1. Department of Bioscience and Bioinformatics, Graduate School of Computer Science and Systems Engineering, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka-shi, Fukuoka 820-8502, Japan;2. Department of Biochemistry & Biophysics, Texas A & M University, College Station, TX 77843-2128, United States;3. Department of Applied Chemistry, Kyushu Institute of Technology, 1-1 Sensui-cho, Tobata-ku, Kitakyushu-shi, Fukuoka 804-8550, Japan;4. Biomedical Informatics Research and Development Center (BMIRC), Kyushu Institute of Technology, 680-4 Kawazu, Iizuka-shi, Fukuoka 820-8502, Japan;1. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210023, China;2. Henan Provincial Key Laboratory of Children''s Genetics and Metabolic Diseases, Children''s Hospital Affiliated to Zhengzhou University, Zhengzhou Children''s Hospital, Zhengzhou 450018, China;1. Chemistry Department, V. P. & R. P. T. P. Science College, Affiliated to Sardar Patel University, Vallabh Vidyanagar 388120, Gujarat, India;2. Department of Biochemistry, Shree Alpesh N. Patel P. G. Institute, Affiliated to Sardar Patel University, Anand 388001, Gujarat, India;1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500 037, Telangana, India;2. Division of Microbiology, CSIR-Central Drug Research Institute, Sitapur Road, Sector 10, Janakipuram Extension, Lucknow, 226031, Uttar Pradesh, India;1. University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia;2. DPU TB Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain;3. Medicines Research Centre, GlaxoSmithKline, Stevenage, Hertfordshire, UK |
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| Abstract: | In an effort to produce new lead antimycobacterial compounds, herein we have reported the synthesis of a sequence of new pyrrolyl benzamide derivatives. The new chemical entities were screened to target enoyl-ACP reductase enzyme, which is one of the key enzymes of M. tuberculosis that are involved in type II fatty acid biosynthetic pathway. Compound 3q exhibited H-bonding interactions with Tyr158, Thr196 and co-factor NAD+ that binds the active site of InhA. All the pyrrolyl benzamide compounds were evaluated as inhibitors of M. tuberculosis H37Rv as well as inhibitors of InhA. Among them, few representative compounds were tested for mammalian cell toxicity on the human lung cancer cell-line (A549) and MV cell line that presented no cytotoxicity. Five of these compounds exhibited a good activity against InhA. |
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| Keywords: | Pyrroles Tuberculosis Enoyl-ACP reductase InhA GALAHAD |
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