Mode Action Prediction of Butein as Antibacterial Oral Pathogen against Enterococcus faecalis ATCC 29212 and an Inhibitor of MurA Enzyme: In Vitro and In Silico Study

Title:Mode Action Prediction of Butein as Antibacterial Oral Pathogen against Enterococcus faecalis ATCC 29212 and an Inhibitor of MurA Enzyme: In Vitro and In Silico Study

Volume: 18 Issue: 7

Author(s): Mieke Hemiawati Satari*, Ameta Primasari, Hendra Dian Adhita Dharsono, Eti Apriyanti, Maria Matoetina Suprijono, Yetty Herdiyati and Dikdik Kurnia*

Affiliation:

• Department of Oral Biology, Faculty of Dentistry, Universitas Padjadjaran, Sumedang,Indonesia

• Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Sumedang,Indonesia

Keywords: Butein, oral bacteria, enterococcus faecalis, mura, myrmecodia pendans, in vitro, in silico.

Abstract:

Background: The MurA enzyme, enolpyruvyl UDP-N-acetylglucosamine transferase, is one of the targeted proteins by antibiotics for effective treatment of diseases provided by pathogenic bacteria. It plays a key role in the cell wall biosynthesis of Gram-positive bacteria such as Enterococcus faecalis. Butein is a flavonoid that showed antioxidant and anticancer activities, but recently it is a promising antibacterial agent and reported can inhibit E. faecelis, Eschericia coli, and Mycobacterium tuberculosis. It was isolated from medicinal plants, including Sarang Semut (Myrmecodia pendans). However, the molecular mechanism of butein inhibits bacteria that is no clear.

Objective: This study aims to predict the molecular action of the butein against MurA, catalyzing the first step of peptidoglycan biosynthesis.

Material and Methods: Butein isolation used a combinational separation technique and characterization using spectroscopic methods. Then, in silico method used was virtual screening using programs including Autodock Vina in PyRx, protein. plus, and ligplots. Butein and UDP-N-acetylglucosamine (UNAG as a positive control) act as ligand were subject binding to 3KQJ MurA as protein. To evaluate in vitro antibacterial activity, we used the Kirby-Bauer method.

Results: Butein from M. pendans is a potential compound to inhibit the MurA with binding affinity - 7.6 kcal.mol-1. It is lower than UNAG but higher than Fosfomycin as a MurA inhibitor. Butein attaches to MurA in the same position as UNAG so that it concludes that both is a competitive inhibitor. Meanwhile, in vitro study showed that butein inhibits the E. faecalis growth with inhibit zone of 8.37 mm at 1 mg/ml.

Conclusion: Butein as a potent antibacterial agent through blocking MurA enzyme in cell wall formation.

Cite this article as:

Satari Hemiawati Mieke *, Primasari Ameta , Dharsono Dian Adhita Hendra, Apriyanti Eti , Suprijono Matoetina Maria , Herdiyati Yetty and Kurnia Dikdik*, Mode Action Prediction of Butein as Antibacterial Oral Pathogen against Enterococcus faecalis ATCC 29212 and an Inhibitor of MurA Enzyme: In Vitro and In Silico Study, Letters in Drug Design & Discovery 2021; 18 (7) . https://dx.doi.org/10.2174/1570180818666210122163009