Review on Current Development of Hydantoin-Based Antimicrobial Agents and Its in Silico Analysis towards Staphylococcus Aureus Serine Protease SplA 4mvn Protein

Keng, Xin Yi (2021) Review on Current Development of Hydantoin-Based Antimicrobial Agents and Its in Silico Analysis towards Staphylococcus Aureus Serine Protease SplA 4mvn Protein. Final Year Project (Bachelor), Tunku Abdul Rahman University College.

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Abstract

Among heterocyclic compounds, hydantoin valuable scaffold being as the great interest in medicinal chemistry field to develop novel drug molecules. The objectives of this study is to review the works regarding antimicrobial activity of hydantoin derivatives and conducted in silico ADMET analysis and molecular docking for novel designed hydantoin-based compounds. All information were acquired from several popular databases such as ACS, PubMed, ScienceDirect, Google Scholar, Springer and other published materials such as books and dissertations by using certain keywords. The present review was summarize various mono-, di-, tri-, tetra- and heterocyclic substituents hydantoin derivatives with its antimicrobial activity, mechanistic pathway, chemical sources of diverse bacteria strains, structure characterization methods, methods of antimicrobial assay. control agent used, yield and purity percentage. However, there are few limitations observed from literature reviews. For instances, some paper lack of information regarding yield and purity percent, number of replications, chemical sources of bacteria strains and even control agent not used in certain antimicrobial testing. On the other hand, a series of novel monosubstituted and disubstituted hydantoin derivatives were designed and carried out in-silico study on these novel hydantoin-based compounds. In this study, different pharmacokinetics parameters and drug-likeness properties were examined through AdmetSAR 2.0 program and Molinspiration server. Moreover, ligand compounds were docked against S.aureus serine protease SplA 4MVN protein that retrieved from Protein data bank by using Discovery studio program and Autodock software. Besides, gentamicin was used as positive control to validate the results. Docking results showed that compounds 4c(iv), 4b(iv), 4e(iv), 4d(iv) and 4c(i) are the best five binding models. Lastly, compound 4e(iv) is remarkable drug candidates against S. aureus serine protease SplA 4MVN target protein due to it is orally bioavailable, well performed in ADME properties, non-toxicity and good binding models with low docking score, -5.91 kcal/mol and 0.05 mM inhibition constant. Lastly, the significance of this study is to discover more hydantoin derivatives as potent antimicrobial agents.