Marine brown algae (Sargassum wightii) derived 9-hydroxyhexadecanoic acid: A promising inhibitor of α-amylase and α-glucosidase with mechanistic insights from molecular docking and its non-target toxicity analysis

• Published in: South African journal of botany 2023-10, Vol.161, p.627-637
• Main Authors: Paramasivam, Deepak, Meyyazhagan, Arun, Thiyagarajulu, Nathiya, Arumugasamy, Karthiga, Balasubramanian, Balamuralikrishnan, Alanazi, Amer M., Rengasamy, Kannan R.R.
• Format: Article
• Language: English
• Subjects: ADME; In silico docking; Palmitic acid; Sargassum wightii; toxicity analysis; α-amylase; α-glucosidase
• ISSN: 0254-6299; 1727-9321
• DOI: 10.1016/j.sajb.2023.08.064

•Marine brown agae (Sargassum wightii) has revealed its potential effects.•Palmitic acid scored good docking values against α-amylase and α-glucosidase.•ADME score of palmitic acid has recorded good activity.•Non-target toxicity assays proved that potential pharmaceutical effects. Jeopardized glucose hemostasis leads to cronic metaboic disorder like Diabetes mellitus and it is predicted to occur in ∼700 million people in the coming 20 years. Our study aims to isolate Palmitic acid (C16H32O3), 9-Hydroxyhexadecanoic acid metabolite from Sargassum wightii to inhibit alpha-amylase and alpha-glucosidase to reduce postprandial hyperglycemia and decline the risk of diabetes. High docking score of palmitic acid with both α-amylase and α-glucosidase is observed in in-silico molecular docking analysis, in comparison to commercially available drug acarbose. The three hydrogen bond in palmitic acid interacts with the important amino acids like Arg195, Lys200 and Asp300 in Glide XP docking mode for alpha-amylase. For α-glucosidase, quantum-polarized ligand docking (QPLD) was used with similar three hydrogen bond interactions. Both docking studies showed significant binding interaction of palmitic acid with α-amylase (−5.66 and −5.14 (Kcal/mol)) and with α-glucosidase (−4.52 and −3.51(Kcal/mol)) with respect to the standard, acarbose docking score. The bioactive palmitic acid isolated from the brown alga, Sargassum wightii is already seen to inhibit digestive enzyme with non-target property in Artemia nauplii and zebra fish embryos. Further studies are required to investigate its role in in vivo antidiabetic effects due to its non-toxic and digestive enzyme inhibitory properties. It can be recommended in additional pharmaceutical studies to develop novel therapeutics to manage diabetes mellitus.