Antiplasmodial, beta-haematin inhibition, antitrypanosomal and cytotoxic activity in vitro of novel 4-aminoquinoline 2-imidazolines


Musonda, CC; Yardley, V; de Souza, RCC; Ncokazi, K; Egan, TJ; Chibale, K; (2008) Antiplasmodial, beta-haematin inhibition, antitrypanosomal and cytotoxic activity in vitro of novel 4-aminoquinoline 2-imidazolines. Organic & biomolecular chemistry, 6 (23). pp. 4446-4451. ISSN 1477-0520 DOI: https://doi.org/10.1039/b813007h

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Abstract

A novel series of 4-aminoquinoline-containing 2-imidazolines were synthesized via a one-pot 3-component condensation reaction of amine, aldehyde and isocyanoacetate. The products were obtained in high yield as well as purity and were evaluated directly against two strains of Plasmodium falciparum and Trypanosoma brucei. Compound 21 was the most active across all parasites with ED50 = 3.3 nM against a chloroquine (CQ)-sensitive 3D7 strain, ED50 = 33 nM against a CQ-resistant K1 strain and ED50 = 70 nM against T. brucei. Several compounds were able to inhibit formation of beta-haematin in vitro, suggesting haemozoin formation in the malaria parasite as a possible target. On the other hand, evaluation against a human KB cell line revealed that the compounds were generally non-cytotoxic to the host cells.

Item Type: Article
Keywords: ANTIMALARIAL-DRUG DISCOVERY, MULTICOMPONENT REACTIONS, COMBINATORIAL, LIBRARIES, PLASMODIUM-FALCIPARUM, RESISTANCE, MECHANISM, CHLOROQUINE, DERIVATIVES, FERROQUINE, CHEMISTRY, Animals, Antiprotozoal Agents, chemical synthesis, chemistry, pharmacology, toxicity, Drug Design, Hemeproteins, antagonists & inhibitors, Humans, Imidazolines, chemical synthesis, chemistry, pharmacology, toxicity, KB Cells, Plasmodium falciparum, drug effects, Quinolines, chemistry, Trypanosoma brucei brucei, drug effects
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
PubMed ID: 19005606
Web of Science ID: 261744800023
URI: http://researchonline.lshtm.ac.uk/id/eprint/6010

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