Synthesis of solution-phase combinatorial library of 4,6-diamino-1,2-dihydro-1,3,5-triazine and identification of new leads against A16V+S108T mutant dihydrofolate reductase of Plasmodium falciparum

Tirayut VilaivanNeungruthai SaesaengseerungDeanpen JarprungSumalee KamchonwongpaisanWorachart SirawarapornYongyuth YuthavongChulalongkorn UniversityThailand National Center for Genetic Engineering and BiotechnologyMahidol University2018-07-242018-07-242003-01-17Bioorganic and Medicinal Chemistry. Vol.11, No.2 (2003), 217-224096808962-s2.0-0037449359https://repository.li.mahidol.ac.th/handle/20.500.14594/20773An efficient method to synthesize solution-phase combinatorial library of 1-aryl-4,6-diamino-1,2-dihydro-1,3,5-triazine was developed. The strategy involved an acid-catalyzed cyclocondensation between arylbiguanide hydrochlorides and carbonyl compounds in the presence of triethyl orthoacetate as water scavenger. A 96-membered combinatorial library was constructed from 6 aryl biguanides and 16 carbonyl compounds. Screening of the library by iterative deconvolution method revealed two candidate leads which are equally active against wild-type Plasmodium falciparum dihydrofolate reductase, but are about 100-fold more effective against the A16V+S108T mutant enzyme as compared to cycloguanil. © 2002 Elsevier Science Ltd. All rights reserved.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyChemistryPharmacology, Toxicology and PharmaceuticsSynthesis of solution-phase combinatorial library of 4,6-diamino-1,2-dihydro-1,3,5-triazine and identification of new leads against A16V+S108T mutant dihydrofolate reductase of Plasmodium falciparumArticleSCOPUS10.1016/S0968-0896(02)00344-9