Discovery of rigid biphenyl <i>Plasmodium falciparum</i> DHFR inhibitors using a fragment linking strategy
Marie Hoarau, Patpanat Sermmai, Thaveechai Varatthan, Ratthiya Thiabma, Tararat Jantra, Roonglawan Rattanajak, Danoo Vitsupakorn, Jarunee Vanichtanankul, Siriporn Saepua, Yongyuth Yuthavong, Chawanee Thongpanchang, Sumalee Kamchonwongpaisan
Abstract
DHFR, high selectivity against the human isoform, drug-like lipophilicity and metabolic stability. Compound 4 and its ester derivative 3 kill blood stage TM4/8.2 parasite at nM concentrations while showing no toxicity against Vero cells.
Topics & Concepts
Fragment (logic)Plasmodium falciparumCytotoxicityChemistryBiphenylDrug discoveryStereochemistryDrugCombinatorial chemistryComputational biologyBiologyMalariaBiochemistryIn vitroPharmacologyComputer scienceImmunologyOrganic chemistryProgramming languageMalaria Research and ControlComputational Drug Discovery MethodsHIV/AIDS drug development and treatment