ANALYSIS OF THERAPEUTICAL POTENTIAL OF NOVEL XANTHONES AND AL. LIED STRUCTURETHROUGH RATIONAL DRUG DESIGN

Abstract

A library of 300 representative xanthones was built. A well-established drug target Plasmodium falciparuni DHFR was docked against the preceding chemical database using Molegro Virtual Docker 5.0. The resulting interaction profiles of the top scorers were studied. The top scorers were I ,3,7-trihydroxy-2-(2-hydroxy-3-methylbut-3-enyl)-4-(3-methylbut-2-enyl)-xanthone (X- 5), 7-Deoxysterigmatocystin (X-113A) and 1-O-f3-D-glucopyranosyl-3,5-dihydroxy-8- methoxyxanthone (X-164B). Further it was revealed that hits X5 and X113 have contact footprint similar to known active and have a greater chance of success in biochemical screening. For experimental verification for this work eleven different xanthone scaffolds have been synthesized by a novel protocol based on multi-component reactions. By using this simple, yet diversity enabling methodology, we were able to bring a change at scaffold and substitutent level. All synthesize molecules has high purity profile and moderate to good yield. We believe that actual biochemical screening (future plan) of these scaffolds will helpful in designing new lead against malarial chemotherapy