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. Preprints2024, 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
Narayanasamy, P.; Crick, D.C. A Novel and Polymeric Inhibitor of MenA against Mycobacterium tuberculosis. Preprints2024, 2024010325. https://doi.org/10.20944/preprints202401.0325.v1
APA Style
Narayanasamy, P., & Crick, D.C. (2024). A Novel and Polymeric Inhibitor of MenA against Mycobacterium tuberculosis. Preprints. https://doi.org/10.20944/preprints202401.0325.v1
Chicago/Turabian Style
Narayanasamy, P. and Dean C. Crick. 2024 "A Novel and Polymeric Inhibitor of MenA against Mycobacterium tuberculosis" Preprints. 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.
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.
