| Title: | Bio-Mechanism of Catechin as Pheromone Signal Inhibitor: Prediction of Antibacterial Agent Action Mode by In Vitro and In Silico Study |
| Author(s): | Kurnia D; Ramadhanty ZF; Ardani AM; Zainuddin A; Dharsono HDA; Satari MH; |
| Address: | "Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Padjadjaran, Sumedang 45363, Indonesia. Department of Conservative Dentistry, Faculty of Dentistry, Universitas Padjadjaran, Bandung 40132, Indonesia. Department of Oral Biology, Faculty of Dentistry, Universitas Padjadjaran, Bandung 40132, Indonesia" |
| DOI: | 10.3390/molecules26216381 |
| ISSN/ISBN: | 1420-3049 (Electronic) 1420-3049 (Linking) |
| Abstract: | "The utilization of medicinal plants has long been explored for the discovery of antibacterial agents and the most effective mechanisms or new targets that can prevent and control the spread of antibiotic resistance. One kind of bacterial cell wall inhibition is the inactivation of the MurA enzyme that contributes to the formation of peptidoglycan. Another approach is to interfere with the cell-cell communication of bacteria called the Quorum sensing (QS) system. The blocking of auto-inducer such as gelatinase biosynthesis-activating pheromone (GBAP) can also suppress the virulence factors of gelatinase and serine protease. This research, in particular, aims to analyze lead compounds as antibacterial and anti-QS agents from Gambir (Uncaria gambir Roxburgh) through protein inhibition by in silico study. Antibacterial agents were isolated by bioactivity-guided isolation using a combination of chromatographic methods, and their chemical structures were determined by spectroscopic analysis methods. The in vitro antibacterial activity was evaluated by disc diffusion methods to determine inhibitory values. Meanwhile, in the in silico analysis, the compound of Uncaria gambir was used as ligand and compared with fosfomycin, ambuic acid, quercetin, and taxifolin as the standard ligand. These ligands were attached to MurA, GBAP, gelatinase, and serine proteases using Autodock Vina in PyRx 0.8 followed by PYMOL for combining the ligand conformation and proteins. plus programs to explore the complex, and visualized by Discovery Studio 2020 Client program. The antibacterial agent was identified as catechin that showed inhibitory activity against Enterococcus faecalis ATCC 29212 with inhibition zones of 11.70 mm at 10%, together with MIC and MBC values of 0.63 and 1.25 mug/mL, respectively. In the in silico study, the molecular interaction of catechin with MurA, GBAP, and gelatinase proteins showed good binding energy compared with two positive controls, namely fosfomycin and ambuic acid. It is better to use catechin-MurA (-8.5 Kcal/mol) and catechin-gelatinase (-7.8 Kcal/mol), as they have binding energies which are not marginally different from quercetin and taxifolin. On the other hand, the binding energy of serine protease is lower than quercetin, taxifolin, and ambuic acid. Based on the data, catechin has potency as an antibacterial through the inhibition of GBAP proteins, gelatinase, and serine protease that play a role in the QS system. This is the first discovery of the potential of catechin as an alternative antibacterial agent with an effective mechanism to prevent and control oral disease affected by antibiotic resistance" |
| Keywords: | Anti-Bacterial Agents/*chemistry/*pharmacology Catechin/*chemistry/*pharmacology Hydrogen Bonding Microbial Sensitivity Tests Molecular Conformation Molecular Docking Simulation Molecular Dynamics Simulation Molecular Structure Pheromones/*chemistry/*phar; |
| Notes: | "MedlineKurnia, Dikdik Ramadhanty, Zenika Febian Ardani, Aprilina Mora Zainuddin, Achmad Dharsono, Hendra Dian Adhita Satari, Mieke Hemiawati eng Switzerland 2021/11/14 Molecules. 2021 Oct 22; 26(21):6381. doi: 10.3390/molecules26216381" |
