Application:
• Use of databases to identify potential new anti-malarial drugs
Malaria is a disease caused by parasitic protozoans of the genus Plasmodium
- The life cycle of the parasite requires both a human and mosquito host – hence the disease is transmitted via mosquito bites
- The maturation and development of the parasite in both human and mosquito host is coordinated by specific enzymes
- By targeting these enzymes for inhibition, new anti-malarial drugs and medications can be produced
Scientists have sequenced the genome of infectious species of Plasmodium and used it to determine the parasite’s proteome
- From the proteome, enzymes involved in parasitic metabolism have been identified as potential targets for inhibition
These enzymes may be screened against a bioinformatic database of chemicals to identify potential enzyme inhibitors
- Once a promising compound is identified, it may be chemically modified to improve its binding affinity and lower its toxicity
- In one particular study, over 300,000 chemicals were screened to identify 19 new chemicals that might function as inhibitors
An alternative method by which potential new anti-malarial medications can be synthesised is via rational drug design
- Rational drug design involves using computer modelling techniques to invent a compound that will function as an inhibitor
- Using combinatorial chemistry, a compound is synthesised that is complementary to the active site of the target enzyme
Plasmodium Life Cycle and Anti-Malarial Drugs
Link: Antimalarial Drug Efficacy Map