Amaning Danquah, Cynthia; (2016) Phytochemical and antimycobacterial studies on selected medicinal plants. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Tuberculosis (TB) is an infectious disease caused by the pathogen Mycobacterium tuberculosis. Tuberculosis was first declared as a global health emergency in 1993 but is still a health crisis worldwide because of the emergence of extensively drug-resistant strains of M. tuberculosis coupled with the increased risk of infection in immune-compromised people and also by the fact that at least one third of the human population are latently infected with the TB causing bacilli. New, safer and more effective antimycobacterial compounds with novel mechanisms of action are urgently needed for treating resistant forms of tuberculosis. This has led to a renewed research interest in natural products, which offer an outstanding source of diverse bioactive chemical scaffolds with the hope of discovering novel anti-mycobacterial leads. This thesis describes phytochemical studies on the genera Allium and Andrographis. The antibacterial activity of the crude extracts, various fractions and isolated compounds were evaluated. Antibacterial studies were carried out using a panel of Gram-positive, Gram-negative and acid fast group of bacterial species including M. aurum, M. bovis BCG, M. tuberculosis H37Rv and multidrug-resistant clinical isolates of M. tuberculosis. Furthermore, analogues of naturally isolated disulfides from the genus Allium were synthesized and evaluated for antibacterial activity. Eukaryotic cytotoxicity was estimated in order to determine the therapeutic selectivity index of the selected compounds. In addition, inhibition of both drug efflux and biofilm formation was observed at the whole-cell phenotypic level. These analogues have demonstrated anti-TB activity with the lowest MIC being 4 mg/L. They also exhibited whole cell multidrug efflux and biofilm inhibitory effect. These findings would serve as useful contribution to the development of novel anti-TB drugs.

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