DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF MORPHOLINE, PIPERIDINE AND PHENYL DERIVATIVES OF QUINAZOLINONE AS HSP90 ATPASE INHIBITORS

Suby T. Baby*, Shailendra Sharma, Sreenivas Enaganti and Roby P. Cherian

ABSTRACT

Hsp90 plays a major role in the oncogenic proteostasis where the over expressed levels of Hsp90 are found in various cancers constituting its role in growth and survival of malignant cells, thus making Hsp90 as an important molecular target in cancer therapeutics. Hence, the discovery and development of novel chemical scaffolds targeting Hsp90, with superior anticancer activity remain an important priority in the cancer field. Here in our study describes the synthesis, biological evaluation of novel quinazolinone derivatives ability to function as anticancer agents on MCF-7 human breast cancer cell line by MTT assay and their potential to suppress Hsp90 ATPase activity by Malachite green assay. Further, docking are carried out to know the binding modes of the compounds and validated by structure based pharmacophore modeling studies which reveals the important structural features responsible for ligand binding.

Keywords: Cancer, docking, Hsp90, malignant, pharmacophore, quinazolinone.