Antimalarial Drug Discovery at NCNPR
Malaria is a life-threatening disease caused by infection with intracellular protozoan parasites of the genus Plasmodium that are transmitted to people through the bites of infected mosquitoes.
This parasitic disease is still considered a major threat to the public health especially in the tropical and subtropical regions of the world despite the global efforts to eradicate or control malaria.
Plasmodium falciparum is one of the four species of Plasmodium that cause malaria in humans. It is transmitted by the female Anopheles mosquito. Malaria caused by this species is the most severe form of malaria with the highest rates of complications and mortality.
In vitro screening of natural product extracts from various sources (plants, microbes, marine) for antimalarial activity is an important component of the Drug Discovery and Development program at NCNPR for the identification of potential new drug candidates with antimalarial activity.
A multidirectional approach is followed for discovery of new antimalarials
- Screening of extracts through an in vitro high throughput method with cultures of drug sensitive and drug resistant strains of malaria parasite (P. falciparum)
- Bioassay guided fractionation of active extracts and isolation of active constituents
- Screening of isolated compound libraries through in vitro method
- Screening of antimalarial activity of compound libraries effective on a specific target or a specific pathway (identified through a target or enzymatic assay or computational method)
- Assessment of therapeutic index
- Understanding the structure activity relationship (SAR)
- In vivo efficacy in a P. berghei infected mouse model
Antimicrobial Drug Discovery Program
Invasive fungal infections are a serious health problem killing over 1,000,000 people worldwide every year. Current antifungal drugs are inadequate, and new therapeutic strategies are greatly needed that can reduce drug toxicity, improve potency, and overcome drug resistance. At the NCNPR, the goal of our antifungal drug discovery program is to discover new antifungal agents that target novel fungal pathways. We are also working on identifying compounds that potentiate the activity of clinically used antifungal drugs, especially for drugs that have lost efficacy in drug-resistant pathogens. We are utilizing a comprehensive drug discovery approach that includes cell-based screening of natural product samples, isolation of pure compounds by bioassay guided fractionation, chemical optimization to improve potency, in vivo efficacy studies in animal models, and mechanistic evaluation of lead compounds at the molecular level. We also have an antibacterial screening program at the NCNPR aimed at discovering antibacterial compounds that can be developed into new drugs for treating antibiotic-resistant infections, which kill over 20,000 people in the U.S. alone each year. While not as extensive as our antifungal program, all of our in-house capabilities are available for the antibacterial discovery program for preclinical evaluation of lead compounds.
Our capabilities include (click list items for more information):