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.