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Tytuł:
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Design, synthesis and biological evaluation of 6-aryl-1,6-dihydro-1,3,5-triazine-2,4-diamines as antiplasmodial antifolates.
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Autorzy:
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Lourens AC; CSIR Biosciences, Meiring Naude Road, Pretoria, 0001 Gauteng, South Africa. , School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
Gravestock D; CSIR Biosciences, Meiring Naude Road, Pretoria, 0001 Gauteng, South Africa. , Jealott's Hill International Research Centre, Bracknell, Berkshire RG42 6EY, UK.
van Zyl RL; Pharmacology Division, Department of Pharmacy and Pharmacology, WITS Research Institute for Malaria (WRIM), Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown 2193, South Africa.
Hoppe HC; CSIR Biosciences, Meiring Naude Road, Pretoria, 0001 Gauteng, South Africa. , Rhodes University, Grahamstown 6140, South Africa.
Kolesnikova N; CSIR Biosciences, Meiring Naude Road, Pretoria, 0001 Gauteng, South Africa. .
Taweechai S; BIOTEC, National Science and Technology Development Agency, Thailand Science Park, Pathumthani 12120, Thailand.
Yuthavong Y; BIOTEC, National Science and Technology Development Agency, Thailand Science Park, Pathumthani 12120, Thailand.
Kamchonwongpaisan S; BIOTEC, National Science and Technology Development Agency, Thailand Science Park, Pathumthani 12120, Thailand.
Rousseau AL; CSIR Biosciences, Meiring Naude Road, Pretoria, 0001 Gauteng, South Africa. and Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, Private Bag 3, PO WITS, 2050, South Africa.
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Źródło:
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Organic & biomolecular chemistry [Org Biomol Chem] 2016 Aug 16; Vol. 14 (33), pp. 7899-911.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Original Publication: Cambridge, UK : Royal Society of Chemistry, c2003-
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MeSH Terms:
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Drug Design*
Antimalarials/*pharmacology
Diamines/*pharmacology
Folic Acid Antagonists/*pharmacology
Plasmodium falciparum/*drug effects
Triazines/*pharmacology
Antimalarials/chemical synthesis ; Antimalarials/chemistry ; Diamines/chemical synthesis ; Diamines/chemistry ; Dose-Response Relationship, Drug ; Folic Acid Antagonists/chemical synthesis ; Folic Acid Antagonists/chemistry ; Molecular Structure ; Parasitic Sensitivity Tests ; Structure-Activity Relationship ; Triazines/chemical synthesis ; Triazines/chemistry
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Substance Nomenclature:
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0 (Antimalarials)
0 (Diamines)
0 (Folic Acid Antagonists)
0 (Triazines)
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Entry Date(s):
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Date Created: 20160802 Date Completed: 20180125 Latest Revision: 20180125
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Update Code:
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20240104
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DOI:
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10.1039/c6ob01350c
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PMID:
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27477595
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The design, synthesis and biological evaluation of a series of 6-aryl-1,6-dihydro-1,3,5-triazine-2,4-diamines is described. These compounds exhibited in vitro antiplasmodial activity in the low nanomolar range against both drug sensitive and drug resistant strains of P. falciparum, with 1-(3-(2,4-dichlorophenoxy)propyl)-6-phenyl-1,6-dihydro-1,3,5-triazine-2,4-diamine hydrochloride identified as the most potent compound from this series against the drug resistant FCR-3 strain (IC50 2.66 nM). The compounds were not toxic to mammalian cells at therapeutic concentrations and were shown to be inhibitors of parasitic DHFR in a biochemical enzyme assay.
