Antileishmanial and antitrypanosomal activity of symmetrical dibenzyl-substituted α,β-unsaturated carbonyl-based compounds.

Alkhaldi, A. A., De Koning, H. P. and Bukhari, S. N. A. (2019) Antileishmanial and antitrypanosomal activity of symmetrical dibenzyl-substituted α,β-unsaturated carbonyl-based compounds. Drug Design, Development and Therapy, 13, pp. 1179-1185. (doi:10.2147/DDDT.S204733) (PMID:31118564) (PMCID:PMC6500899)

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Abstract

Human African Trypanosomiasis (HAT) and leishmaniasis are two of the most neglected challenging tropical diseases, caused by the kinetoplastid parasites and species, respectively. For both of these complex disease spectra, treatment options are limited and threatened by drug resistance, justifying urgent new drug discovery efforts. In the present study we investigated the antitrypanosomal and antileishmanial activity of a series of 21 symmetrical α,β-unsaturated carbonyl-based compounds, each featuring two 3-methoxybenzene attached to a central cyclohexanone, tetrahydro-4-pyranone scaffold or 4-piperidone ring. Structure-activity relationships were explored with respect to substitution on positions 3, 4 and 6 of the terminal 3-methoxybenzyl groups, and seven types of central ring. Compounds and , showed broad anti-kinetoplastid activity against all species and strains tested. Compound featuring -methyl-4-piperidone was found to be the most potent analog and therefore can serve as a potential lead for the development of new drug candidates for trypanosomiasis and leishmaniasis.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:De Koning, Professor Harry
Authors: Alkhaldi, A. A., De Koning, H. P., and Bukhari, S. N. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Drug Design, Development and Therapy
Publisher:Dove Medical Press
ISSN:1177-8881
ISSN (Online):1177-8881
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Drug Design, Development and Therapy 13:1179-1185
Publisher Policy:Reproduced under a Creative Commons License

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