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Lead selection of antiparasitic compounds from a focused library of benzenesulfonyl derivatives of heterocycles

Pagliero, Romina J. and Kaiser, Marcel and Brun, Reto and Nieto, Marcelo J. and Mazzieri, María R.. (2017) Lead selection of antiparasitic compounds from a focused library of benzenesulfonyl derivatives of heterocycles. Bioorganic & medicinal chemistry, 27 (17). pp. 3945-3949.

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Abstract

A library of 89 synthetic benzenesulfonyl derivatives of heterocycles with drug-like properties was assayed for in vitro antiparasitic activity and the results were added to our previously reported derivatives for a comprehensive SAR evaluation. Four compounds showed an IC50 between 0.25 and 3μM against Leishmania donovani and low cytotoxicity. Compound G{16} (1-(2,3,5,6-tetramethylphenylsulfonyl)-2-methylindoline), was particularly interesting with an IC50 similar to the reference drug miltefosine. Seven compounds showed an IC50 below 6µM against Trypanosoma cruzi, and three of them (E{3}, E{9} and G{3}) were identified as lead scaffolds for further optimization based on their activity-toxicity profile. Two promising structures (B{15} and G{15}) showed moderate inhibitory activity against Plasmodium falciparum. In general, the presence of a benzenesulfonyl moiety improves the antiparasitic activity of the heterocycles included in this study (with the exception of Trypanosoma brucei rhodesiense), validating the criteria used in the selection of the privileged structures and diversification used to generate this library. SAR analysis showed that the presence of lipophilic and electron withdrawing groups were favorable for the antiparasitic activity.
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:Kaiser, Marcel and Brun, Reto
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:0968-0896
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:07 Dec 2017 10:12
Deposited On:07 Dec 2017 10:12

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