Rational Drug Design


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•  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

malarial drugs

Link:  Antimalarial Drug Efficacy Map