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Abstract

SYNTHESIS AND BIOLOGICAL EVALUATION OF METAL COMPLEXES DERIVED FROM 3-METHYL-NHYDROXYBENZAMIDINE AS POTENT INHIBITORS OF THYMIDYLATE KINASE FROM MYCOBACTERIUM TUBERCULOSIS

Hitendra Kumar Lautre*, Royana Singh, Kishore Patil, Taibi Ben Hadda, HafidYoussouffi, Prasenjit Bose, Mayank Krishna Kulshrestha, Chandreshwar PrasadSinha, Ajai Kumar Pillai, Snigdha Das

ABSTRACT

Present work investigate the synthesis of Co(II), Cr(II) and Zn(II) complexes of 3-methyl-N-hydroxybenzamidine as potent and selective inhibitors of Mycobacterium tuberculosis thymidylate kinase (MtTMK). Structural properties were confirmed by NMR, IR, UV-vis, Mass spectral, elemental data and thermogravimetric analysis. The inhibitory concentration at 50% (IC50) and inhibition constant Ki of each compound were measured against the thymidylate kinase. The IC50 of all the compounds ranges 37-86 μM, Ki obtained was 54-195 μM against MtTMK. Antibacterial activity of all the compounds exhibited high selectivity and potency against the selected bacterial strains, compared of ampicillin, which was confirmed by the MIC values. DNA cleavage and antioxidant activities exhibited that all compounds have multi target properties. Antioxidant activities of ligand was higher compared to metal complexes.

Keywords: Thymidylate kinase inhibitor, tuberculosis, amidine metal complexes, M.tuberculosis.


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