Article
Version 1
Preserved in Portico This version is not peer-reviewed
A Novel and Polymeric Inhibitor of MenA against Mycobacterium tuberculosis
Version 1
: Received: 3 January 2024 / Approved: 4 January 2024 / Online: 4 January 2024 (09:49:21 CET)
How to cite: Narayanasamy, P.; Crick, D. C. A Novel and Polymeric Inhibitor of MenA against Mycobacterium tuberculosis. Preprints 2024, 2024010325. https://doi.org/10.20944/preprints202401.0325.v1 Narayanasamy, P.; Crick, D. C. A Novel and Polymeric Inhibitor of MenA against Mycobacterium tuberculosis. Preprints 2024, 2024010325. https://doi.org/10.20944/preprints202401.0325.v1
Abstract
Menaquinone is one of the major lipoquinones involved in the respiratory chains of bacteria, which includes ubiquinone. Menaquinone is an essential component in the electron transfer process and ATP synthesis especially in some Gram-positive bacteria including Mycobacterium tuberculosis (M. Tb). However, mammals utilize ubiquinone in the analogous electron transfer processes, and do not synthesize menaquinone. In the biosynthesis of menaquinone, MenA is an important enzyme, which is involved in the conversion of 1,4-dihydroxy-2-napthoate to demethylmenaquinone via prenyl transferase activity. Therefore MenA is chosen as a drug target in determining the inhibitor. While designing and screening MenA inhibitors we observed that benzophenone derivatives showed high coordination with enzymes in transition state and interrupted the growth of M. Tb moderately. In addition, diphenyl ether derivatives also showed moderate MIC and IC50 results. Therefore, to improve the biological activity we synthesized a polymeric compound having both benzophenone and diphenyl ether groups. In addition, a hydrophilic functional group was introduced into the polymeric compound to enhance the biological activity. The synthesized polymeric inhibitor showed improved MIC and IC50 values to inhibit the M. tb infection.
Keywords
Menaquinone; inhibitor; Mycobacterium tuberculosis; MIC; IC50
Subject
Chemistry and Materials Science, Medicinal Chemistry
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Comments (0)
We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.
Leave a public commentSend a private comment to the author(s)
* All users must log in before leaving a comment