in silico discovery of potential inhibitors against Dipeptidyl Peptidase-4: A major biological target of Type-2 diabetes mellitus

Published on: 26th February, 2020

OCLC Number/Unique Identifier: 8560723476

Objectives: Type-2 diabetes mellitus, caused by impaired secretion of insulin, is becoming one of the health hazardous threats to human lives across the world. Its prevalence is rising with time. In this study, 2750 phytochemicals, that are considered to have great ability to eliminate diseases caused by different viruses and bacteria, are obtained from different medicinal plants and discovery of inhibitors through in silico method was performed against Dipeptidyl peptidase-4 (DPP4). Method: The pharmacological assessment and pharmacokinetics of phytochemicals, molecular docking and density functional theory (DFT) analysis helped to explore the inhibitory action of phytochemicals against DPP4. Total forty-nine phytochemicals were screened initially to reduce the number of compounds to be analyzed further based on a threshold of binding affinity ≥ -5.5 kcal/mol and were considered for further computational studies to analyze their inhibitory effects for DPP4. For comparison and validation of the results of present study, various previously reported and experimentally validated compounds were docked with the DPP4. For these dockings, binding affinity was predicted and compared with those of phytochemicals to check if these phytochemicals are competent enough to be used as an inhibitor in the treatment of diabetes mellitus in the future. Results: Only four phytochemicals showed binding affinity greater than those of experimentally validated compounds. These included two phytochemicals from Silybum marianum, i.e. Diprenyleriodictyol and Taxifolin and while other two phytochemicals from Santolina insularis and Erythrina Varigatae i.e. Papraline and Osajin respectively. The reactivity levels for these four phytochemicals with the binding site residues of DPP4 were obtained by DFT based analysis, in which ELUMO, EHOMO and band energy gap were computed. Conclusion: Based on these results, it is concluded that these four phytochemicals, after passing through in vitro and in vivo validation, can be utilized as potential DPP4 inhibitors as they have strong properties as compared to those of various experimentally validated inhibitors.
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