Synthesis, Characterization and Response of Newer Benzamidine Analogues against Porphyromonas gingivalis mediated Peri-Implantitis

Abstract

Evidence suggests development of various therapeutic strategies against peri-implantitis ranging from plant extracts to synthetic molecules, but the development of resistance and associated side effects motivates the investigators to explore some new therapeutic moieties. Therefore, the present study was aimed to perform the synthesis, characterization, in vitro cytotoxicity analysis and in vitro antimicrobial activity of novel benzamidine analogues (NBA) against Porphyromonas gingivalis mediated peri-implantitis. To achieve the objectives of present study, 12 newer benzamidine analogues (NBA) were designed and subjected to molecular docking against Kgp-lysine specific cysteine proteinases gingipain K (PDB ID: 4RBM). Thus in present study, novel benzamidine analogues (NBA) were synthesized, followed by characterization (using attenuated total reflectance infrared, 1H & 13C NMR and direct infusion mass spectral data), in vitro antimicrobial activity (MIC and MBC) of NBA against P. gingivalis (using micro broth dilution method) and in vitro cytotoxicity analysis of NBA against HEK 293 cells (using MTT assay). The study offered successful synthesis of three NBA (3a-c) and elucidated their structures. All the synthesized NBA exhibited good antimicrobial activity against P. gingivalis with MIC value ranged between 31.25-250 µg/mL. Also, all NBA exhibited weak/negligible cytotoxicity against HEK 293 cells at 7.81 µg/mL. In conclusion, this study has led to the successful synthesis of effective peri-implantitis inhibitors with no significant toxicity. Present study recommends that, in future, the synthesized NBA should be further evaluated for their clinical importance in the peri-implantitis.