Molecular Docking study, synthesis and biological evaluation of Schiff bases as Hsp90 inhibitors

SAYAN DUTTA GUPTA; D. SNIGDHA; GISELA I. MAZAIRA; MARIO D. GALIGNIANA; C.V.S. SUBRAHMANYAM; N.L. GOWRISHANKAR; N.M. RAGHAVENDRA

BIOMEDICINE & PHARMACOTHERAPY = BIOMEDECINE & PHARMACOTHERAPIE.

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

Año: 2014 vol. 68 p. 369 - 376

0753-3322

Heat shock protein 90 (Hsp90) is an emerging attractive target for the discovery of novel cancer therapeutic agents. Docking methods are powerful in silico tools for lead generation and optimization. In our mission to rationally develop novel effective small molecules against Hsp90, we predicted the potency of our designed compounds by Sybyl surflex Geom X docking method. The results of the above studies revealed that Schiff bases derived from 2,4-dihydroxy benzaldehyde/5-chloro-2,4-dihydroxybenzaldehyde demonstrated effective binding with the protein. Subsequently, a few of them were synthesized (1?10) and characterized by IR, 1HNMR and mass spectral analysis. The synthesized molecules were evaluated for their potential to suppress Hsp90 ATPase activity by Malachite Green assay. The anticancer studies were performed by 3-(4,5-dimethythiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method. The software generated results was in satisfactory agreement with the evaluated biological activity.