Singh, Kamaljit ; Kaur, Hardeep ; Chibale, Kelly ; Balzarini, Jan ; Little, Susan ; Bharatam, Prasad V. (2012) 2-Aminopyrimidine based 4-aminoquinoline anti-plasmodial agents. Synthesis, biological activity, structure–activity relationship and mode of action studies European Journal of Medicinal Chemistry, 52 . pp. 82-97. ISSN 0223-5234
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Official URL: http://doi.org/10.1016/j.ejmech.2012.03.007
Related URL: http://dx.doi.org/10.1016/j.ejmech.2012.03.007
Abstract
2-Aminopyrimidine based 4-aminoquinolines were synthesized using an efficacious protocol. Some of the compounds showed in vitro anti-plasmodial activity against drug-sensitive CQS (3D7) and drug-resistant CQR (K1) strains of Plasmodium falciparum in the nM range. In particular, 5-isopropyloxycarbonyl-6-methyl-4-(2-nitrophenyl)-2-[(7-chloroquinolin-4-ylamino)butylamino] pyrimidine depicted the lowest IC50 (3.6 nM) value (56-fold less than CQ) against CQR strain. Structure–activity profile and binding with heme, μ-oxo-heme have been studied. Binding assays with DNA revealed better binding with target parasite type AT rich pUC18 DNA. Most compounds were somewhat cytotoxic, but especially cytostatic. Molecular docking analysis with Pf DHFR allowed identification of stabilizing interactions.
| Item Type: | Article |
|---|---|
| Source: | Copyright of this article belongs to Elsevier B.V. |
| Keywords: | 2-Aminopyrimidine; 4-Aminoquinolines; DHFR Inhibitor; CT DNA Interaction; DHPM. |
| ID Code: | 116508 |
| Deposited On: | 12 Apr 2021 09:57 |
| Last Modified: | 12 Apr 2021 09:57 |
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