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dc.contributor.authorYongyuth Yuthavongen_US
dc.contributor.authorTirayut Vilaivanen_US
dc.contributor.authorNetnapa Chareonsethakulen_US
dc.contributor.authorSumalee Kamchonwongpaisanen_US
dc.contributor.authorWorachart Sirawarapornen_US
dc.contributor.authorRachel Quarrellen_US
dc.contributor.authorGordon Loween_US
dc.contributor.otherThailand National Center for Genetic Engineering and Biotechnologyen_US
dc.contributor.otherChulalongkorn Universityen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherUniversity of Oxforden_US
dc.date.accessioned2018-09-07T09:08:13Z-
dc.date.available2018-09-07T09:08:13Z-
dc.date.issued2000-07-13en_US
dc.identifier.citationJournal of Medicinal Chemistry. Vol.43, No.14 (2000), 2738-2744en_US
dc.identifier.issn00222623en_US
dc.identifier.other2-s2.0-0034644146en_US
dc.identifier.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=0034644146&origin=inwarden_US
dc.identifier.urihttp://repository.li.mahidol.ac.th/dspace/handle/123456789/25862-
dc.description.abstractThe Ala16Val+Ser108Thr (A16V+S108T) mutant of the Plasmodium falciparum dihydrofolate reductase (DHFR) is a key mutant responsible for cycloguanil-resistant malaria due to steric interaction between Val-16 and one of the C-2 methyl groups of cycloguanil. 4,6-Diamino-1,2-dihydrotriazines have been prepared, in which both methyl groups of cycloguanil are replaced by H or by H and an alkyl or phenyl group, and their inhibition constants against wild-type and mutant DHFR determined. The S108T mutation is considered to decrease cycloguanil binding further through the effect on the orientation of the p-chlorophenyl group. By moving the p-chloro-substituent to the m-position in the chlorophenyl group, the activity against the A16V+S108T mutant enzyme is improved, and this effect is reinforced by the p-chloro substituent in the 3,4-dichlorophenyl group. A lead compound has been found with inhibitory activity similar to that of cycloguanil against the wild-type DHFR and about 120-fold more effective than cycloguanil against the A16V+S108T mutant enzyme. The activity of this compound against P. falciparum clone (T9/94 RC17) which harbors the A16V+S108T DHFR is about 85-fold greater than cycloguanil.en_US
dc.rightsMahidol Universityen_US
dc.source.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=0034644146&origin=inwarden_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.subjectPharmacology, Toxicology and Pharmaceuticsen_US
dc.titleDevelopment of a lead inhibitor for the A16V+S108T mutant of dihydrofolate reductase from the cycloguanil-resistant strain (T9/94) of Plasmodium falciparumen_US
dc.typeArticleen_US
dc.rights.holderSCOPUSen_US
dc.identifier.doi10.1021/jm0009181en_US
Appears in Collections:Scopus 1991-2000

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