The Potential of Several alkaloids of Rhizophora stylosa To Enhance Destruction Cell Wall Mechanism Against Bacterial Resistance

Abstract

The resistance of the beta-lactams became a major factor that contributes to mortality caused by bacterial infection. The combination of clavulanate acid and penicillin groups has been used widely as a solution against bacterial resistance. However, several cases reported that clavulanate acid caused an allergy response. The Rhizophora stylosa; is one of the mangrove subspecies widely investigated due to its empirical use in traditional medicine. This study aimed to predict the potential of alkaloid compounds of these plants as a candidate for co-antibacterial agents against bacterial resistance. This study used several alkaloids that have been found in R. Stylosa (sanguinarine, muscimol, glycosin, ergobasine, mescaline, pilosine, and nordihydrocapsaicin) as a subject of this study. The beta-lactamases (PDB ID: 6NVU) and penicillin-binding proteins (PDB ID: 3UY6) were used as targeted proteins. The drug-likeness and pharmacokinetics of compounds were analyzed using Swiss ADME. Meanwhile, the affinity of ligands was predicted using Autodock Vina. The root means square distance (RMSD) value (<2 A) and the binding cavity of drugs (amoxicillin and clavulanate acid) were used as parameters of validation. This study resulted that these alkaloids have good drug-likeness and high gastrointestinal absorption. However, prediction of other parameters (BBB permeant, Pgp substrate, and inhibition of cytochrome enzyme) show that only muscimol, mescaline, and pilosine didn’t affect these parameters. The affinity value of four compounds (sanguinarine, glycosin, ergobasine, and mescaline) indicated better affinity in both proteins. Moreover, the combination use of amoxicillin with these four compounds increases the affinity of amoxicillin. These conclude that some alkaloids of R. Stylosa could potentially be used as co-drugs with amoxicillin to both increase activity and prevent bacterial resistance 

 Keywords:  In-silico, R.Stylosa, alkaloid, bacterial resistance