Synthesis and biological evaluation of 2-arylbenzimidazoles targeting Leishmania donovani

Bioorg Med Chem Lett. 2015 May 1;25(9):1933-7. doi: 10.1016/j.bmcl.2015.03.027.

Leena Keurulainen ¹, Antti Siiskonen ¹, Abedelmajeed Nasereddin ², Dmitry Kopelyanskiy ², Nina Sacerdoti-Sierra ², Teppo O Leino ¹, Päivi Tammela ³, Jari Yli-Kauhaluoma ¹, Charles L Jaffe ⁴, Paula Kiuru ⁵

Affiliations

1 Faculty of Pharmacy, Division of Pharmaceutical Chemistry and Technology, University of Helsinki, Viikinkaari 5 E, PO Box 56, FI-00014 Helsinki, Finland.
2 Department of Microbiology and Molecular Genetics, IMRIC, Hebrew University-Hadassah Medical School, PO Box 12272, Jerusalem 9112102, Israel.
3 Faculty of Pharmacy, Division of Pharmaceutical Biosciences, Centre for Drug Research, University of Helsinki, Viikinkaari 5 E, PO Box 56, FI-00014 Helsinki, Finland.
4 Department of Microbiology and Molecular Genetics, IMRIC, Hebrew University-Hadassah Medical School, PO Box 12272, Jerusalem 9112102, Israel. Electronic address: [email protected].
5 Faculty of Pharmacy, Division of Pharmaceutical Chemistry and Technology, University of Helsinki, Viikinkaari 5 E, PO Box 56, FI-00014 Helsinki, Finland. Electronic address: [email protected].

PMID: 25827525 DOI: 10.1016/j.bmcl.2015.03.027

Abstract

A set of 56 2-arylbenzimidazoles was designed, synthesized and tested against Leishmania donovani amastigotes. The left- and right-hand side rings of the molecule, as well as the amide linker were modified. Structurally different derivatives were screened on L. donovani axenic amastigotes at concentrations of 5, 15 and 50 μM, and the ten most active derivatives were selected for further testing. 2-Arylbenzimidazole derivative 24 was active against L. donovani-infected THP-1 cells showing 46% Parasite inhibition at 5 μM.

Keywords

2-Arylbenzimidazoles; Antileishmanial activity; Biological activity; Leishmania donovani; Medicinal chemistry.

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