Design,synthesis, biological evaluation of substituted benzofurans as DNA gyraseB inhibitors of Mycobacterium tuberculosis |
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| Institution: | 1. Department of Chemistry, Sri Krishnadevaraya University, Anantapur 515055, India;2. DBT-HTS, Piramal Entreprises Limited, Nirlon Complex, Goregaon East, Mumbai 400063, India;3. New Generation Materials Lab (NGML), Department of Science & Humanities, VFSTR University, Vadlamudi-522 213, Andra Pradesh, India;4. Centre for Organic and Medicinal Chemistry, VIT University, Vellore, 632 014 Tamil Nadu, India;5. Plant Biotechnology Division, School of Biosciences and Technology, VIT University, Vellore, 632014 Tamil Nadu, India;1. Department of Chemistry, Acharya Nagarjuna University, Nagarjuna Nagar 522510 Andhra Pradesh, India;2. Department of Chemistry, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur, Andhra Pradesh 522502, India;3. Department of Chemistry, Shree Velagapudi Ramakrishna Memorial College, Nagaram, Andhra Pradesh 522268, India |
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| Abstract: | DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase and is a well-established and validated target for the development of novel therapeutics. By adapting the medium throughput screening approach, we present the discovery and optimization of ethyl 5-(piperazin-1-yl) benzofuran-2-carboxylate series of mycobacterial DNA gyraseB inhibitors, selected from Birla Institute of Technology and Science (BITS) database chemical library of about 3000 molecules. These compounds were tested for their biological activity; the compound 22 emerged as the most active potent lead with an IC50 of 3.2 ± 0.15 μM against Mycobacterium smegmatis DNA gyraseB enzyme and 0.81 ± 0.24 μM in MTB supercoiling activity. Subsequently, the binding of the most active compound to the DNA gyraseB enzyme and its thermal stability was further characterized using differential scanning fluorimetry method. |
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| Keywords: | Tuberculosis DNA gyraseB Antibacterial activity Cytotoxicity |
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