DOI: 10.5176/2345-783X_PHARMA15.01
Authors: Sukhbir Lal Khokra, ReetuSaini, Sunainaaggarwal
Abstract:
The computational approach has been developed as practical solution which eliminates the problem of diverse sampling. Benzothiazoles have been found to mimic the ATP-competitive binding of genistein and quercetin to tyrosine kinase. In order to find a potent anticancer agent and for better understanding of the molecular interactions of inhibitors with Tyrosine kinase and Pvs25 ookinete protein, the four different series of benzothiazoles were analyzed by molecular docking. The PDB ID: 2QU5 was used with the same mechanism of actions as well as same inhibitors in the present studies. In four series of forty three compounds, the derivatives of 2-(1,3-diphenyl-1H-pyrazole-4-yl)benzothiazole (3a-3m) showed best mol dock score values range between -159.95 to -128.82 and maximum number of H-bond interactions with the receptor. The best compounds 3h and 3j showed highest mol dock score values -159.95 and -156.98 with H-bond interaction values three and five respectively. The substituted (2-chloroquinolin-3-yl) -1, 3 -benzothiazole derivatives (4a-4l) showed only moderate mol dock score values. The pyrazole based Schiff bases of benzothiazoles (5a-5j) also showed good mol dock score values. The compound 5h having 2, 4, 6-trihydroxy functional group was found to be best in this series with mol dock score value -148.03. The quinoline based Schiff bases (6a-6h) again showed very low mol dock score values among all the series. From above results, it is observed that compounds 3h, 3j and 5h are the best tyrosine kinase inhibitors agents and may be helpful in designing of potentially active therapeutic agents. The maximum activity is observed in compounds having hydroxyl or methoxy substituted phenyl at pyrazole ring in 2-position of benzothiazole ring. The replacement of pyrazole with quinoline decreases the activity in both non-Schiff base as well as Schiff base derivatives.
Keywords: Benzothiazole, Tyrosine kinase nhibitors, Docking Molegro
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