title: Exploration of Scaffolds from Natural Products with Antiplasmodial Activities, Currently Registered Antimalarial Drugs and Public Malarial Screen Data.
abstract: 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.
authors.affiliation: South African Medical Research Council Bioinformatics Unit, South African National Bioinformatics Institute, University of the Western Cape, Cape Town 7535, South Africa. segieyeh@sanbi.ac.za.
authors.forename: Samuel
authors.initials: S
authors.lastname: Egieyeh
authors.affiliation: School of Pharmacy, University of the Western Cape, Cape Town 7535, South Africa. jsyce@uwc.ac.za.
authors.forename: James
authors.initials: J
authors.lastname: Syce
authors.affiliation: South African Medical Research Council Bioinformatics Unit, South African National Bioinformatics Institute, University of the Western Cape, Cape Town 7535, South Africa. alan@sanbi.ac.za.
authors.forename: Alan
authors.initials: A
authors.lastname: Christoffels
authors.affiliation: School of Pharmacy, University of the Western Cape, Cape Town 7535, South Africa. sfmalan@uwc.ac.za.
authors.forename: Sarel F
authors.initials: SF
authors.lastname: Malan
mesh_terms: D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry*; D062126:Databases, Chemical; D015195:Drug Design; D055808:Drug Discovery; D006801:Humans; D008288:Malaria / Q000188:drug therapy; D010961:Plasmodium / Q000187:drug effects; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014584:User-Computer Interface
chemical_list: D000962:Antimalarials; D001688:Biological Products; D054852:Small Molecule Libraries
keywords: antimalarial drugs; natural products; scaffold diversity; scaffold tree