Potential Allylpyrocatechol Derivatives as Antibacterial Agent Against Oral Pathogen of <em>S. sanguinis</em> ATCC 10,556 and as Inhibitor of MurA Enzymes: in vitro and in silico Study

Dikdik Kurnia

Geofanny Hutabarat

Devi Windaryanti

Tati Herlina

Yetty Herdiyati

Mieke Satari

^{Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Padjadjaran, Sumedang, Indonesia}

^{Department of Pediatric Dentistry, Faculty of Dentistry, Universitas Padjadjaran, Bandung, Indonesia}

^{Department of Oral Biology, Faculty of Dentistry, Universitas Padjadjaran, Bandung, Indonesia}

Correspondence: Dikdik Kurnia Email dikdik.kurnia@unpad.ac.id

Received 2020 Apr 7; Accepted 2020 Jul 7.

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Abstract

Background

Streptococcus sanguinis is Gram-positive bacteria that contribute to caries. Many antibacterial agents are resistant against bacteria so that the discovery of new antibacterial agents is a crucial issue. Mechanism of antibacterial agents by disrupting cell wall bacteria is a promising target to be developed. One of the enzymes contributing to the cell wall is MurA enzyme. MurA is an enzyme catalyzing the first step of peptidoglycan biosynthesis in the cell wall formation. Inhibiting MurA is an effective and efficient way to kill the bacteria. Source of bioactive compounds including the antibacterial agent can be found in natural product such as herbal plant. Piper betle L. was reported to contain active antibacterial compounds. However, there is no more information on the antibacterial activity and molecular mechanism of P. betle’s compound against S. sanguinis.

Purpose

The study aims to identify antibacterial constituents of P. betle L. and evaluate their activities through two different methods including in vitro and in silico analysis.

Materials and Methods

The antibacterial agent was purified by bioactivity-guided isolation with combination chromatography methods and the chemical structure was determined by spectroscopic methods. The in vitro antibacterial activity was evaluated by disc diffusion and dilution methods while the in silico study of a compound binds on the MurA was determined using PyRx program.

Results

The antibacterial compound identified as allylpyrocatechol showed inhibitory activity against S. sanguinis with an inhibition zone of 11.85 mm at 1%, together with MIC and MBC values of 39.1 and 78.1 μg/mL, respectively. Prediction for molecular inhibition mechanism of allylpyrocatechols against the MurA presented two allylpyrocatechol derivatives showing binding activity of −5.4, stronger than fosfomycin as a reference with the binding activity of −4.6.

Conclusion

Two allylpyrocatechol derivatives were predicted to have a good potency as a novel natural antibacterial agent against S. sanguinis through blocking MurA activity that causes disruption of bacterial cell wall.

Keywords: Piper betle L., allylpyrocatechol, Streptococcus sanguinis, MurA enzyme

Abstract

Acknowledgments

The authors are grateful to the Ministry of Research, Technology, and Higher Education of the Republic of Indonesia for Grant of Penelitian Magister 2020. This research was supported by Academic Leadership Grant 2020 from Universitas Padjadjaran, Sumedang Indonesia.

Acknowledgments

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