Identification of a potential antimalarial drug candidate from a series of 2-aminopyrazines by optimization of aqueous solubility and potency across the parasite life cycle

Le Manach, Claire and Nchinda, Aloysius T. and Paquet, Tanya and Gonzàlez Cabrera, Diego and Younis, Yassir and Han, Ze and Bashyam, Sridevi and Zabiulla, Mohammed and Taylor, Dale and Lawrence, Nina and White, Karen L. and Charman, Susan A. and Waterson, David and Witty, Michael J. and Wittlin, Sergio and Botha, Mariëtte E. and Nondaba, Sindisiswe H. and Reader, Janette and Birkholtz, Lyn-Marie and Jiménez-Díaz, María Belén and Martínez, María Santos and Ferrer, Santiago and Angulo-Barturen, Iñigo and Meister, Stephan and Antonova-Koch, Yevgeniya and Winzeler, Elizabeth A. and Street, Leslie J. and Chibale, Kelly. (2016) Identification of a potential antimalarial drug candidate from a series of 2-aminopyrazines by optimization of aqueous solubility and potency across the parasite life cycle. Journal of medicinal chemistry, 59 (21). pp. 9890-9905.

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Official URL: http://edoc.unibas.ch/54714/

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Abstract

Introduction of water-solubilizing groups on the 5-phenyl ring of a 2-aminopyrazine series led to the identification of highly potent compounds against the blood life-cycle stage of the human malaria parasite Plasmodium falciparum. Several compounds displayed high in vivo efficacy in two different mouse models for malaria, P. berghei-infected mice and P. falciparum-infected NOD-scid IL-2Rγ(null) mice. One of the frontrunners, compound 3, was identified to also have good pharmacokinetics and additionally very potent activity against the liver and gametocyte parasite life-cycle stages.

Faculties and Departments:	09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) 09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Parasite Chemotherapy (Mäser)
UniBasel Contributors:	Wittlin, Sergio
Item Type:	Article, refereed
Article Subtype:	Research Article
Publisher:	American Chemical Society
ISSN:	0022-2623
Note:	Publication type according to Uni Basel Research Database: Journal article
Identification Number:	doi: 10.1021/acs.jmedchem.6b01265 pmid: 27748596
Last Modified:	20 Oct 2017 06:11
Deposited On:	20 Apr 2017 13:48

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