Rapid Discovery of Aspartyl Protease Inhibitors Using an Anchoring Approach.

ABSTRACT: Pharmacophore searches that include anchors, fragments contributing above average to receptor binding, combined with one-step syntheses are a powerful approach for the fast discovery of novel bioactive molecules. Here, we are presenting a pipeline for the rapid and efficient discovery of aspartyl protease inhibitors. First, we hypothesized that hydrazine could be a multi-valent warhead to interact with the active site Asp carboxylic acids. We incorporated the hydrazine anchor in a multicomponent reaction and created a large virtual library of hydrazine derivatives synthetically accessible in one-step. Next, we performed anchor-based pharmacophore screening of the libraries and resynthesized top-ranked compounds. The inhibitory potency of the molecules was finally assessed by an enzyme acti

SUBMITTER: Konstantinidou M 

PROVIDER: S-EPMC7317454 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature