Affiliation:
1. Department of Pharmaceutical Chemistry, Faculty of Natural Sciences, University of the Western Cape, Private Bag
X17, Bellville 7535, South Africa
Abstract
Abstract:
The treatment and management of tuberculosis (TB) is a major global concern. Approved
drugs for the treatment of TB, to date, have displayed various modes of action which can be grouped
into radical releasing and non-radical releasing anti-TB agents. Radical releasing agents are of special
interest because they diffuse directly into the mycobacterium cell wall, interact with the host cell
DNA, causing DNA strand breakages and fatal destabilization of the DNA helix inhibiting nucleic
acid synthase. As a therapeutic agent with the aforementioned activity, nitroimidazoles and most especially
bicyclic nitroimidazoles are currently in clinical use for the treatment of tuberculosis. However,
the approved drugs, pretomanid (PR) and delamanid (DE) are limited in their nitric oxide radical
(NO•) releasing abilities to cause effective bactericidity. It is believed that their bactericidal activity
can be improved by harnessing alternative strategies to increase NO• release. The last decade has witnessed
the strategic inclusion of NO-donors into native drugs to improve their activities and/or reverse
resistance. The rationale behind this strategy is the targeting of NO• release at specific therapeutic
sites. This review, therefore, aims to highlight various radical releasing agents that may be effective in
the treatment of TB. The review also investigates various structural modifications to PR and DE and
suggests alternative strategies to improve NO• release as well as some applications where NO-donor
hybrid drugs have been used with good therapeutic effect.
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmacology,General Medicine