Srinu M
Jawaharlal Nehru Technological University Hyderabad
India.
Title: Design, Synthesis and Docking Study of Some Novel Isatin- Quinoline Hybrids as Potential Antitubercular Agents
Biography
Biography: Srinu M
Abstract
A hybrid pharmacophore approach was deployed to design and synthesize new series of isatin- quinoline hybrids. All the new series of hybrids (6 a-l) were investigated for molecular docking study against enoyl ACP reductase enzyme. The docking study was performed on 22 newly designed isatin analogs by using Auto Dock 4.2 on the active site of crystal structure of enoyl ACP reductase enzyme (PDB ID: 4TZK). The binding modes of these analogs were calculated based on the two parameters such as binding energy and inhibition constant. The results shown that all the isatin analogs were in the range between -6.43 kcal/mol and -9.08 kcal/mol. Based on the results obtained by the docking study twelve new series of Isatin- quinoline hybrid molecules were synthesized and characterized by physical and spectral analyses (FT-IR, 1H-NMR, 13C NMR and Mass spectroscopy). According to the docking study compound 6h has highest binding affinity with a binding energy of -9.08 kcal/mol and predicted inhibition constant was 221.75 nanomolar. This compound exhibited well established hydrophobic bonds with amino acid Tyr 158 and the co factor NAD 500 in the receptor active pocket and fortunately these two are responsible for the enzyme activity. All the hybrids were evaluated for their in vitro antitubercular activity against drug resistant strains of Mycobacterium tuberculosis (MTB) by using micro dilution method and their inhibitory (MIC) and bactericidal (MBC) activity was determined. Compound 6h has the good inhibitory (0.09 mg/L) and bactericidal (0.30 mg/L) activity as compared with the reference drug, isoniazide (0.03 mg/L & 0.05 mg/L).