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Keywords = menaquinone biosynthesis inhibitor

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30 pages, 15400 KiB  
Review
Bioenergetics of Mycobacterium: An Emerging Landscape for Drug Discovery
by Iram Khan Iqbal, Sapna Bajeli, Ajit Kumar Akela and Ashwani Kumar
Pathogens 2018, 7(1), 24; https://doi.org/10.3390/pathogens7010024 - 23 Feb 2018
Cited by 53 | Viewed by 12964
Abstract
Mycobacterium tuberculosis (Mtb) exhibits remarkable metabolic flexibility that enables it to survive a plethora of host environments during its life cycle. With the advent of bedaquiline for treatment of multidrug-resistant tuberculosis, oxidative phosphorylation has been validated as an important target and a vulnerable [...] Read more.
Mycobacterium tuberculosis (Mtb) exhibits remarkable metabolic flexibility that enables it to survive a plethora of host environments during its life cycle. With the advent of bedaquiline for treatment of multidrug-resistant tuberculosis, oxidative phosphorylation has been validated as an important target and a vulnerable component of mycobacterial metabolism. Exploiting the dependence of Mtb on oxidative phosphorylation for energy production, several components of this pathway have been targeted for the development of new antimycobacterial agents. This includes targeting NADH dehydrogenase by phenothiazine derivatives, menaquinone biosynthesis by DG70 and other compounds, terminal oxidase by imidazopyridine amides and ATP synthase by diarylquinolines. Importantly, oxidative phosphorylation also plays a critical role in the survival of persisters. Thus, inhibitors of oxidative phosphorylation can synergize with frontline TB drugs to shorten the course of treatment. In this review, we discuss the oxidative phosphorylation pathway and development of its inhibitors in detail. Full article
(This article belongs to the Special Issue Mechanisms of Mycobacterium tuberculosis Pathogenesis)
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23 pages, 654 KiB  
Review
Vitamin K2 in Electron Transport System: Are Enzymes Involved in Vitamin K2 Biosynthesis Promising Drug Targets?
by Michio Kurosu and Eeshwaraiah Begari
Molecules 2010, 15(3), 1531-1553; https://doi.org/10.3390/molecules15031531 - 10 Mar 2010
Cited by 132 | Viewed by 19259
Abstract
Aerobic and anaerobic respiratory systemsallow cells to transport the electrons to terminal electron acceptors. The quinone (ubiquinone or menaquinone) pool is central to the electron transport chain. In the majority of Gram-positive bacteria, vitamin K2 (menaquinone) is the sole quinone in the [...] Read more.
Aerobic and anaerobic respiratory systemsallow cells to transport the electrons to terminal electron acceptors. The quinone (ubiquinone or menaquinone) pool is central to the electron transport chain. In the majority of Gram-positive bacteria, vitamin K2 (menaquinone) is the sole quinone in the electron transport chain, and thus, the bacterial enzymes catalyzing the synthesis of menaquinone are potential targets for the development of novel antibacterial drugs. This manuscript reviews the role of vitamin K in bacteria and humans, and especially emphasizes on recent aspects of menaquinones in bacterial electron transport chain and on discoveries of inhibitor molecules targeting bacterial electron transport systems for new antibacterial agents. Full article
(This article belongs to the Special Issue Vitamins)
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