Molecular docking study, synthesis and biological evaluation of Mannich bases as Hsp90 inhibitors

SAYAN DUTTA GUPTA S, BOMMAKA MK, MAZAIRA GI, GALIGNIANA MD, SATYA CV, NARYANASAMY S, GOWRISHANKAR L, RAGHAVENDRA NM

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2015 vol. 80 p. 253 - 259

0141-8130

The ubiquitously expressed heat shock protein 90 is an encouraging target for the developmentof novel anticancer agents. In a program directed towards uncovering novel chemical scaffoldsagainst Hsp90, we performed molecular docking studies using Tripos-Sybyl drug designingsoftware by including the required conserved water molecules. The results of the docking studiespredicted Mannich bases derived from 2,4-dihydroxy acetophenone/5-chloro 2,4-dihydroxyacetophenone as potential Hsp90 inhibitors. Subsequently, a few of them were synthesized (1-6)and characterized by IR, 1H NMR, 13C NMR and mass spectral analysis. The synthesizedMannich compounds were evaluated for their potential to suppress Hsp90 ATPase activity by thecolorimetric Malachite green assay. Subsequently, the molecules were screened for theirantiproilferative effect against PC3 pancreatic carcinoma cells by adopting the 3-(4,5-dimethythiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method. The activityprofile of the identified derivatives correlated well with their docking results.