Inhibitory of Gingipains from Porphyromonas Gingivalis by Cratoxylum Cochinchinense: an In-Silico Study

Tan, Jia Yin (2021) Inhibitory of Gingipains from Porphyromonas Gingivalis by Cratoxylum Cochinchinense: an In-Silico Study. Final Year Project (Bachelor), Tunku Abdul Rahman University College.

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Abstract

Porphyromonas gingivalis is a keystone pathogen in the onset and progression of periodontal disease. It is involved in the inflammation and in the tissue destruction during periodontal disease and it is found to be linked with several diseases, including Alzheimer’s disease, cardiovascular disease, diabetes mellitus and rheumatoid arthritis. Rgp and Kgp are gingipains, the trypsin-like cysteine proteinases which are one of the most important virulence factors for this bacterium. A number of studies have investigated the inhibitory effects of natural products such as flavonoids against gingipains. In the present study we aim to investigate the inhibitory effects of xanthones from C. cochinchinense against Rgp and Kgp via in silico approach, as well as to analyze the molecular interactions between the xanthones and the active site of Rgp and Kgp. Molecular docking indicated that among the 17 selected phytochemicals, the cudratricusxanthone E-Rgp complex and cudratricusxanthone E-Kgp complex exhibited the most negative binding energy, which were -10.22 kcal/mol and -13.12 kcal/mol respectively. The positive control used for both Rgp and Kgp was TLCK. Interestingly, the binding energies of both these xanthones-complexes were lower than that of the TLCK-complexes. Besides, both cudratricusxanthone E and TLCK interacted with the important catalytic residues of both gingipains. A higher number of interactions could contribute to the higher inhibitory activity for cudratricusxanthone E than TLCK against Rgp and Kgp. Furthermore, the presence of polyhydroxyl groups and prenyl side chains may be responsible for the inhibitory effect of cudratricusxanthone E. In short, cudratricusxanthone E may be a potential dual-inhibitor for Rgp and Kgp. This study suggests future research to further justify its inhibitory activity against both gingipains, which may pave way to the development of adjunctive periodontal therapeutic agent.