Exploration of Scaffolds from Natural Products with Antiplasmodial Activities, Currently Registered Antimalarial Drugs and Public Malarial Screen Data

Molecules

James Syce¹  Sarel F. Malan¹  Samuel Egieyeh²  Alan Christoffels² 

[1] School of Pharmacy, University of the Western Cape, Cape Town 7535, South Africa;South African Medical Research Council Bioinformatics Unit, South African National Bioinformatics Institute, University of the Western Cape, Cape Town 7535, South Africa;

关键词: natural products;    antimalarial drugs;    scaffold diversity;    scaffold tree;   

DOI  :  10.3390/molecules21010104

来源: DOAJ

【 摘 要 】

In light of current resistance to antimalarial drugs, there is a need to discover new classes of antimalarial agents with unique mechanisms of action. Identification of unique scaffolds from natural products with in vitro antiplasmodial activities may be the starting point for such new classes of antimalarial agents. We therefore conducted scaffold diversity and comparison analysis of natural products with in vitro antiplasmodial activities (NAA), currently registered antimalarial drugs (CRAD) and malaria screen data from Medicine for Malaria Ventures (MMV). The scaffold diversity analyses on the three datasets were performed using scaffold counts and cumulative scaffold frequency plots. Scaffolds from the NAA were compared to those from CRAD and MMV. A Scaffold Tree was also generated for each of the datasets and the scaffold diversity of NAA was found to be higher than that of MMV. Among the NAA compounds, we identified unique scaffolds that were not contained in any of the other compound datasets. These scaffolds from NAA also possess desirable drug-like properties making them ideal starting points for antimalarial drug design considerations. The Scaffold Tree showed the preponderance of ring systems in NAA and identified virtual scaffolds, which may be potential bioactive compounds.

【 授权许可】

Unknown