In-silico and In-vitro Evaluation of the Anti-diabetic Potential of p-Propoxybenzoic Acid

Background: p-propoxybenzoic acid (p-PBA) is reported as an active chemical constituent of medicinal plants that possess anti-diabetic activity. It is termed a Multiple-Designed Ligand (MDL) having the ability to block more than one enzyme. A molecular docking study justifies the binding ability of p-PBA with acarbose and NaVO4 which were considered standard compounds having the ability to block target enzymes. α-amylase inhibition assay was used as an in-vitro screening model to evaluate the activity of p-PBA against diabetes on an initial basis. Methods: For the molecular docking study, a PDB file of p-PBA was prepared and PDB files of α-amylase (1C8Q), α-glucosidase (5KZW) and PTP1B (5K9W) were procured. p-PBA was docked against the enzymes using the blind docking method. The binding score of p-PBA and standard with enzymes was obtained and compared. The percentage inhibition of an α-amylase enzyme by p-PBA was measured by using a DNS-modified α-amylase inhibition assay and half-maximal inhibitory concentration (IC50) was calculated. Results: p-PBA has a significant inhibitory effect against α-amylase, α-glucosidase, and PTP1B with docking scores of 8.43 ± 0.44 kcal/mol, 9.19 ± 0.49 kcal/mol, and 9.40 ± 0.47 kcal/mol respectively. IC50calculated from the results of α-amylase inhibition assay p-PBA was 56.59 μg/mL. Conclusion: A combination of in-silico and in-vitro methods assessed p-PBA’s anti-diabetic potential on an initial basis. A molecular docking study involving p-PBA concluded the affinity of p-PBA to α-amylase, α-glucosidase, and PTP1B was significantly correlated with the affinity of acarbose and NaVO4. In-vitro α-amylase assay validated the compound’s inhibitory action against the enzyme.