Targeting prolyl tripeptidyl peptidase from Porphyromonas gingivalis with the bioactive compounds from Rosmarinus officinalis

Abstract

Abstract Background Complications in periodontitis and other systemic infections related to Porphyromonas gingivalis poses a serious impediment in the treatment process. This leads to the search of novel target proteins to develop newer drugs against P. gingivalis. Prolyl tripeptidyl peptidase (ptp-A) seem to be a vital protein in P. gingivalis virulence and can be a good target for the novel natural bioactive compounds. Objectives To explore the inhibitory potential of Rosmarinus officinalis biocompounds against the ptp-A of P. gingivalis. Methods Three-dimensional structure of ptp-A was retrieved from the Protein Data Bank with further optimization of both the protein and ligands. In silico inhibitory potential of the selected ligands against ptp-A was done by AutoDock 2.0 and was visualized with Biovia discovery studio visualizing tool with the assessment of the molecular properties of the ligands against ptp-A by molinspiration calculations and drug likeliness. Results High ptp-A inhibitory effect was observed using rosmarinic acid and luteolin with a bonding energy of −9.81 kcal/mol with 10 hydrogen bond interactions and −9.99 kcal/mol with 7 hydrogen bond interactions, respectively. Carnosic acid and p-coumaric acid showed a binding energy of −7.14 kcal/mol and −6.34 kcal/mol, respectively, with 5 hydrogen bond interactions. Molinspiration assessments showed R. officinalis compounds as the best drug candidates with the topological polar surface area scores <140 Å toward the best oral bioavailability. Conclusion The carnosic acid, rosmarinic acid, p-coumaric acid, and luteolin from R. officinalis seem to possess a promising inhibitory effect against ptp-A of Candida albicans suggesting ptp-A as the best target to combat P. gingivalis with further in vivo validation.