Newly designed compounds from scaffolds of known actives as inhibitors of survivin: computational analysis from the perspective of fragment-based drug design.

ABSTRACT: Survivin is an apoptosis suppressing protein linked to different forms of cancer. As it stands, there are no approved drugs for the inhibition of survivin in cancer cells despite a number of promising compounds in clinical trials. This study designed a new set of compounds from fragments of active survivin inhibitors to potentiate their binding with survivin at BIR domain. Three hundred and five (305) fragments made from eight potent inhibitors of survivin were reconstructed to form a new set of compounds. The compounds were optimized using R group enumeration and bioisostere replacement after extensive docking analysis. The optimised compounds were filtered by a validated pharmacophore model to reveal how well they are aligned to the pharmacophore sites. Molecular docking of the well alig

SUBMITTER: Elekofehinti OO 

PROVIDER: S-EPMC8316515 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature