Bioinformatic approach of propolis as an inhibitor of peptidoglycan glycosyltransferase to improve antibacterial agent: An in-silico study

Background: In Indonesia, the prevalence of dental and oral problems is still high at 57.6% in 2018, especially periodontitis at 74.1%. Peptidoglycan is an essential component of the bacterial cell wall. Peptidoglycan glycosyltransferase (PGT) is a protein target that plays a role in transferring lipid disaccharides II to growing glycan chains for bacterial cell wall synthesis. Propolis is a natural ingredient produced by bees and has anti-inflammatory, antibacterial, antiviral and antioxidant properties so that it has the potential to be a natural mouthwash ingredient. One of the antibacterial properties of propolis is to be able to kill and reduce the number of bacteria that cause periodontitis. Purpose: This study aims to investigate the potential of a specific compound of propolis as an inhibitor of protein peptidoglycan glycosyltransferase through bonding interactions. Methods: The method used is an in-silico test in molecular docking with computational software, namely Molegro virtual docker and Discovery Studio visualizer. Results: This study showed the types of bonds between the four compounds, and chlorhexidine as a control showed similar types of bonds, including hydrogen bonds, hydrophobic interactions and unfavourable bonds. The binding energy values of each of the five compounds were pinocembrin -222.166 kJ/mol, hesperetin -230.144 kJ/mol, chrysin -219.45 kJ/mol, caffeic acid phenethyl ester -266.64 kJ/mol and chlorhexidine -362.71 kJ/mol. Conclusion: Caffeic acid phenethyl ester (CAPE) is the most significant potential as an inhibitor of protein peptidoglycan glycosyltransferase and chlorhexidine has the highest binding affinity than the four propolis compounds, followed by caffeic acid phenethyl ester in propolis in silico.

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

Letters in Drug Design & Discovery ◽

10.2174/1570180817999200714104737 ◽

2020 ◽

Vol 17 (12) ◽

pp. 1531-1537

Author(s):

Bella Riyana ◽

Desi Harneti Putri Huspa ◽

Mieke Hemiawati Satari ◽

Dikdik Kurnia

Keyword(s):

Cell Wall ◽

Bacterial Cell ◽

In Silico ◽

Bacterial Activity ◽

Bacterial Cell Wall ◽

Resistant Bacteria ◽

In Silico Studies ◽

In Silico Study ◽

Natural Inhibitor

Background: Currently, infectious diseases caused by pathogenic and resistant bacteria are more challenging for anti-bacterial drug discovery. The discovery of new anti-bacterial 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 anti-bacterial 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 that reportedly contained anti-bacterial agents. The anti-bacterial compounds were isolated by combinations of chromatography methods guided by anti-bacterial activity against bacteria of E. faecalis, S. mutans, and S. sanguinis. The structures of active compounds were characterized by spectroscopic methods, and the anti-bacterial activity was evaluated by the microdilution method (in vitro) combined with molecular docking of the MurA enzyme (in silico). Results: The anti-bacterial flavonoids of catechin were 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 a binding affinity of -8.5 Kcal/mol to MurA which is 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.

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Potential Fatty Acid as Antibacterial Agent against Oral Bacteria of Streptococcus mutans and Streptococcus sanguinis from Basil (Ocimum americanum): In vitro and in silico studies.

Current Drug Discovery Technologies ◽

10.2174/1570163817666200712171652 ◽

2020 ◽

Vol 17 ◽

Author(s):

Yetty Herdiyati ◽

Yonada Astrid ◽

Aldina Amalia Nur Shadrina ◽

Ika Wiani ◽

Mieke Hemiawati Satari ◽

...

Keyword(s):

Cell Wall ◽

Antibacterial Activity ◽

Streptococcus Mutans ◽

Lauric Acid ◽

Bacterial Cell ◽

In Silico ◽

Antibacterial Agent ◽

Bacterial Cell Wall ◽

Ocimum Americanum

Background: Streptococcus mutans and Streptococcus sanguinis are Gram-positive bacteria that cause dental caries. The MurA enzyme is a catalyst in the formation of peptidoglycan in the bacterial cell wall making it ideal as an antibacterial target. Basil (Ocimum americanum) is an edible plant medicine that diverse, very widely spreading, used as herbal for a long time, and it was reported to have pharmacology effect as antibacterial activity. The purpose of this study is to identify antibacterial compounds from O. americanum and analyze their inhibition activity to the MurA enzyme. Methods: Fresh leaves from O. americanum extracted with n-hexane and purified by a combination of column chromatography on normal and reverse phase together with guided by in vitro bioactivity assay against S. mutans ATCC 25175 and S. sanguinis ATCC 10556, respectively, while in silico molecular docking simulation of lauric acid (1) using PyRx 0.8. Results: The structure determination of antibacterial compound by spectroscopic methods resulted in an active compound 1 as lauric acid. The in vitro evaluation of antibacterial activity compound 1 showed the MIC and MBC of 78.13 & 156.3 ppm and 1250 & 2500 ppm against S. sanguinis and in S. mutans, respectively. Further analysis in silico evaluation as MurA Enzyme inhibitor, lauric acid (1) has a binding affinity of -5.2 Kcal/mol those higher than fosfomycin. Conclusion: The lauric acid has potency as a new natural antibacterial agent through the MurA inhibition in bacterial cell wall biosynthesis.

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