Project Lead(s): Solomon Woldeamanuel
In 2015, approximately 3.2 billion people – nearly half of the world’s population – were at risk of malaria.
Sub-Saharan Africa carries a disproportionately high share of the global malaria burden. Some 15 countries (mainly in sub-Saharan Africa) account for 80% of malaria cases and 78% deaths globally.
Drug discovery from natural products for diseases like malaria is both time- and cost-intensive. An efficient approach is to use computer-aided drug design (CADD) through which virtual screening investigates a virtual library of natural products from a database against biological targets linked with disease processes.
The project team sought to develop a web-based, searchable, in-silico database of natural products of Kenya, to provide knowledge and information about the rich diversity of Kenyan flora that may be used in drug discovery.
Information on natural products of Kenya was collected from written literature, including conference proceedings and publications.
The structures of the compounds were drawn and the data collected was used to create a database for design and synthesis of anti-plasmodial lead compounds.
Currently, the database has a total of 1,112 compounds, isolated from diverse natural products of Kenya.
In addition to structures, the database also contains detailed information about the International Union of Pure and Applied Chemistry (IUPAC) name, common name, botanical source and place of collection of the plants from which these compounds are obtained.
One of the key features of the database is the availability of the 3D structures of the compounds, which can be downloaded for use in CADD.
The database is free to access for researchers interested in the chemistry surrounding Kenyan flora. The database is hosted at the mitishamba.uonbi.ac.ke domain.
The database was used to model anti-plasmodial compounds that inhibit Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH).
The project identified three scaffolds, namely benzoxazines, chromones and naphtoquinoes, as the best virtual inhibitors of the P. falciparum dihydroorotate dehydrogenase enzyme – a malaria parasite that can be used for the design of antimalarial lead compounds.
A total of nine synthetically accessible compounds, representing the three classes, were synthesized and the compounds were then tested in vitro to determine their anti-plasmodial activity against chloroquine-sensitive (3D7) and resistant (K1) strains of Plasmodium falciparum.
These three scaffolds need to be optimized through further CADD synthesis and biological evaluation to develop anti-plasmodial compounds.
Scientists in the East African region have requested that the database be expanded to include natural products isolated from the wider flora of the East African region (Kenya, Uganda and Tanzania) and the aim is to do so, once funds become available.