The Potency of Catechin from Gambir (Uncaria gambir Roxb.) as a Natural Inhibitor of MurA (1UAE) Enzyme: In vitro and In silico studies

Abstract

Background: Currently, the infectious disease caused by pathogenic and resistant bacteria is more challenging for antibacterial drug discovery. The discovery of new antibacterial agents developed in many mechanisms includes disruption of the bacterial cell wall formations. The MurA is a key enzyme contributing to the first step of bacterial peptidoglycan biosynthesis and is therefore proposed as an effective bactericidal target. Objective: The purpose of this research is to identify antibacterial compounds from U. gambir Roxb and to predict the potential inhibitory activities against murA enzyme by in silico study. Materials and Methods: Investigation and discovery of new inhibitors of MurA enzyme were conducted on the medicinal plant of Gambir (Uncaria gambir Roxb) and those reported contained antibacterial. The antibacterial compounds were isolated by combinations of chromatography methods guided by antibacterial activity against bacteria of E. faecalis, S. mutans, and S. sanguinis. The structures of active compounds were characterized by spectroscopic methods, and the antibacterial activity was evaluated by the microdilution method (in vitro) combined with molecular docking of the MurA enzyme (in silico). Results: The antibacterial flavonoid of catechin was isolated from U. gambir Roxb with MIC values of 6250 and 12500 ppm, respectively against S. sanguinis and E. faecalis. The in silico study showed that catechin has binding affinity -8.5 Kcal/mol to MurA those higher than fosfomycin as a positive control. Conclusions: The catechin is predicted to have potential as a new natural inhibitor of the MurA enzyme to inhibit bacterial cell wall biosynthesis.

Advances in UDP-N-Acetylglucosamine Enolpyruvyl Transferase (MurA) Covalent Inhibition

“…The problem surrounding fosfomycin, being the only inhibitor commercially available, since its discovery makes increasing number of studies to be carried out to find other covalent inhibitors capable of inhibiting MurA in different types of organisms ( Bachelier et al, 2006 ; Shigetomi et al, 2010 ; Elsebai et al, 2016 ; Hamilton et al, 2020 ; Riyana et al, 2020 ; Petri et al, 2021 ). Thus, the enzyme, being one of the main targets of peptidoglycan biosynthesis, has been mostly studied for the development of covalent inhibitors ( Table 1 ).…”

“…The flavonoid compound catechin from Uncaria gambir Roxb. is a potent natural inhibitor of MurA which prevents the growth of E. faecalis and S. sanguinis ( Riyana et al, 2020 ). Six-tuliposide B is a natural product that shows antibiotic activity against bacterial MurA acting via cnicin mechanism (binding to Cys115 of MurA), and sesquiterpene lactone cnicin also has antibiotic activity ( Bachelier et al, 2006 ; Shigetomi et al, 2010 ).…”

Advances in Research on Chemical Constituents and Their Biological Activities of the Genus Actinidia

“… Part Bioactivity Refs. 139 (+)-Catechin A. arguta [ 41 ] Roots Anti-DPPH radical and inhibiting nitric oxide (in vitro) [ 57 ] Anti-bacteria (in vitro) [ 93 ] 140 (−)-Epi-catechin A. arguta [ 41 ] Roots Anti-DPPH radical and inhibiting nitric oxide (in vitro) [ 57 ] 141 (+)-Afzelechin A. chinensis Planch [ 94 ] Roots 142 (−)- Epi -afzelechin A. chinensis Planch [ 94 ] Roots 143 (+)-Catechin(4 α → 8)(+)-catechin A. chinensis Planch [ 94 ] Roots 144 (−)- Epi -catechin(4 β → 8)(−)-epi-catechin A. chinensis Planch [ 94 ] Roots 145 (+)-Afzelechin(4 α → 8) (+)-afzelechin A. chinensis Planch [ 94 ] Roots 146 (−)- Epi -afzelechin(4 β → 8)(−)-epi-afzelechin A. chinensis Planch [ 94 ] Roots <...>…”

Action mode of ursolic acid as a natural antioxidant and inhibitor of superoxide dismutase

“…[ 6 7 8 ] Some antibacterial, antidiabetic, and anti-inflammatory actions against damage produced by the process of mediating free radicals have been documented, but activity against the enzyme superoxide dismutase (SOD) has not yet been identified. [ 9 ]…”