Universität zu Köln

Basova, Sofia, Wilke, Nathalie, Koch, Jan Christoph, Prokop, Aram, Berkessel, Albrecht ORCID: 0000-0003-0470-7428, Pradel, Gabriele and Ngwa, Che Julius (2020). Organoarsenic Compounds with In Vitro Activity against the Malaria Parasite Plasmodium falciparum. Biomedicines, 8 (8). BASEL: MDPI. ISSN 2227-9059

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Abstract

The rapid development of parasite drug resistance as well as the lack of medications targeting both the asexual and the sexual blood stages of the malaria parasite necessitate the search for novel antimalarial compounds. Eleven organoarsenic compounds were synthesized and tested for their effect on the asexual blood stages and sexual transmission stages of the malaria parasitePlasmodium falciparumusing in vitro assays. The inhibitory potential of the compounds on blood stage viability was tested on the chloroquine (CQ)-sensitive 3D7 and the CQ-resistant Dd2 strain using the Malstat assay. The most effective compounds were subsequently investigated for their effect on impairing gametocyte development and gametogenesis, using the gametocyte-producing NF54 strain in respective cell-based assays. Their potential toxicity was investigated on leukemia cell line Nalm-6 and non-infected erythrocytes. Five out of the 11 compounds showed antiplasmodial activities against 3D7, with half-maximal inhibitory concentration (IC50) values ranging between 1.52 and 8.64 mu M. Three of the compounds also acted against Dd2, with the most active compound As-8 exhibiting an IC(50)of 0.35 mu M. The five compounds also showed significant inhibitory effects on the parasite sexual stages at both IC(50)and IC(90)concentrations with As-8 displaying the best gametocytocidal activity. No hemolytic and cytotoxic effect was observed for any of the compounds. The organoarsenic compound As-8 may represent a good lead for the design of novel organoarsenic drugs with combined antimalarial and transmission blocking activities.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Basova, Sofia UNSPECIFIED UNSPECIFIED UNSPECIFIED Wilke, Nathalie UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Jan Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Prokop, Aram UNSPECIFIED UNSPECIFIED UNSPECIFIED Berkessel, Albrecht UNSPECIFIED orcid.org/0000-0003-0470-7428 UNSPECIFIED Pradel, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Ngwa, Che Julius UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-324261
DOI:	10.3390/biomedicines8080260
Journal or Publication Title:	Biomedicines
Volume:	8
Number:	8
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2227-9059
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Organic Chemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language XANTHURENIC ACID; TRANSMISSION; MOLECULES; DRUGS Multiple languages Medicine, Research & Experimental; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/32426