Evaluation of Antibacterial Potential of Oxadiazole Derivative Compounds Against Peptidyl Arginine Deiminases of P.Gingivalis Using in Silico Molecular Docking and Admet Prediction

Abstract

Background:Periodontitis is a widespread chronic polymicrobial inflammatory condition which is associated with multifactorial causation. Red complex bacteria have a significant role in the pathophysiology of periodontitis. Porphyromonas gingivalis has been termed as keystone pathogen since they play a crucial role for the development of symbiosis by creating a community-wide impact with low-abundance bacteria. Various virulence factors are found in P.gingivalis which includes lipopolysaccharide (LPS), gingipains, fimbriae, pili, lectins, capsule, peptidyl arginine deiminases, collagenases, superoxide dismutases and proteases. The virulence factor under emphasis here in our study is the enzyme Porphyromonas gingivalis peptide arginine deiminases (PPAD).Aim: Our study aimed to identify the potential inhibitors of peptidyl arginine deiminases of P.gingivalis with oxadiazole compounds. Materials and methods: The computerised crystal structure of the receptor molecules and the P.gingivalis peptidyl arginine deiminases (PDB ID: 5AK7) were taken from the protein data bank, and protein processing was carried out in accordance with the accepted procedures and practises around the world. A maximum of six conformers were developed for each of the ligands in order to explore the best-docked conformation between the ligand and protein using the docking technique offered by Auto Dock Vina. To estimate in-silico pharmacokinetic parameters, the Swiss ADME tool was used with the derived chemical structures of the synthesised compounds (1-6) to create their canonical simplified molecular input line entry system (SMILE). Using ProTox II and OSIRIS Property Explorer, the ligands' organ toxicities, toxicological endpoints, and LD50 were deciphered. Amoxicillin, Moxifloxacin, Sulfanilamide, and Sulfamethoxazole, four common medications, were compared to the analyses of the synthesised compounds. Results and discussion: The produced compounds (1-6) were discovered to have minimal binding energies ranging from -6.3 to -8.3 kcal/mol, with compound 2 (-8.3 kcal/mol) producing the best results. This outcome validated the findings of the experimental study that indicated a potential antibacterial in-vitro. The produced compounds may be a viable antibacterial agent against the P.gingivalis strain, according to the overall docking results. The SwissADME prediction findings show that the compounds (2,5,6) completely adhere to Lipinski's rule of five. Conclusion: Results show that all selected ligands (1-6) exhibit better interactions with the target protein within the binding sites. Ligands 2,5, and 6 obey Lipinski’s rule of 5 with low toxicity profile and provide a better interaction score. Compounds with similar functional groups and its interactions can be explored for further studies. The molecule could be further developed and in the future, these drugs could be a better alternative to standard drugs.