Rational drug design approach for overcoming drug resistance: Application to pyrimethamine resistance in malaria

• Main Authors: James H. McKie, Kenneth T. Douglas, Cecil Chan, Simon A. Roser, Robert Yates, Martin Read, John E. Hyde, Michael J. Dascombe, Yongyuth Yuthavong, Worachart Sirawaraporn
• Other Authors: University of Manchester
• Format: Article
• Published: 2018
• Subjects: Biochemistry, Genetics and Molecular Biology; Pharmacology, Toxicology and Pharmaceutics
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/18305
• Institution: Mahidol University

Pyrimethamine acts by selectively inhibiting malarial dihydrofolate reductase-thymidylate synthase (DHFR-TS). Resistance in the most important human parasite, Plasmodium falciparum, initially results from an S108N mutation in the DHFR domain, with additional mutation (most commonly C59R or N51I or b...