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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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Metadata
Document Title
Design, synthesis and biological evaluation of 6-aryl-1,6-dihydro-1,3,5-triazine-2,4-diamines as antiplasmodial antifolates
Author
Lourens A.C.U.,Gravestock D.,Van Zyl R.L.,Hoppe H.C.,Kolesnikova N.,Taweechai S.,Yuthavong Y.,Kamchonwongpaisan S.,Rousseau A.L.
Name from Authors Collection
Affiliations
CSIR Biosciences Meiring Naude Road Pretoria, Gauteng, 0001, South Africa; Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa; Syngenta, Jealott's Hill International Research Centre, Bracknell-Berkshire, RG42 6EY, United Kingdom; 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; Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, 6140, South Africa; BIOTEC, National Science and Technology Development Agency Thailand Science Park, Pathumthani, 12120, Thailand; Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, Private Bag 3 PO WITS 2050, South Africa
Type
Article
Source Title
Organic and Biomolecular Chemistry
ISSN
14770520
Year
2016
Volume
14
Issue
33
Page
7899-7911
Open Access
All Open Access, Hybrid Gold, Green
Publisher
Royal Society of Chemistry
DOI
10.1039/c6ob01350c
Abstract
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. © 2016 The Royal Society of Chemistry.
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
License
CC BY
Rights
Author
Publication Source
Scopus