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Medicinal Chemistry

Author(s): Godfrey R. Matowane, Limpho M. Ramorobi, Samson S. Mashele, Susanna L. Bonnet, Anwar E.M. Noreljaleel, Shasank S. Swain, Tshepiso J. Makhafola and Chika I. Chukwuma*

DOI: 10.2174/1573406418666220620144601

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Novel Caffeic Acid - Zinc Acetate Complex: Studies on Promising Antidiabetic and Antioxidative Synergism Through Complexation

Page: [147 - 162] Pages: 16

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Abstract

Background: The role of Zn(II) in storage, insulin secretion and function has been documented, while plant phenolics have antioxidant and other pharmacological credence.

Objective: The study aimed at synthesizing a novel medicinal Zn(II) complex. The medicinal properties of zinc(II) and caffeic acid were considered in synthesizing a novel complex with promising and improved antioxidant and anti-hyperglycaemic attributes.

Methods: Complex synthesis was done using a 1:2 molar ratio of zinc acetate and caffeic acid and structurally characterized using NMR, FT-IR, high resolution-mass spectroscopy and HPLC. Its cellular toxicity was assessed in Chang liver cells and L-myotubes. In vitro, cellular, and isolated tissue models were used to evaluate the antioxidant and anti-hyperglycaemic properties of the complex relative to its precursors. Molecular docking was used to investigate the interaction with insulin signalling target proteins: GLUT-4 and protein kinase B (Akt/PKB).

Results: Zinc(II) and caffeic acid interacted via Zn:O4 coordination, with the complex having one moiety of Zn(II) and 2 moieties of caffeic acid. The complex showed in vitro radical scavenging, α- glucosidase and α-amylase inhibitory activity up to 2.6 folds stronger than caffeic acid. The ability to inhibit lipid peroxidation (IC50 = 26.4 μM) and GSH depletion (IC50 = 16.8 μM) in hepatocytes was comparable to that of ascorbic acid (IC50 = 24.5 and 29.2 μM) and about 2 folds stronger than caffeic acid. Complexation improved glucose uptake activity of caffeic acid in L-6 myotubes (EC50 = 23.4 versus 169 μM) and isolated rat muscle tissues (EC50 = 339 versus 603 μM). Molecular docking showed better interaction with insulin signalling target proteins (GLUT-4 and Akt/PKB) than caffeic acid. The complex was not hepatotoxic or myotoxic.

Conclusion: Data suggest a synergistic antioxidant and anti-hyperglycaemic potential between zinc and caffeic acid, which could be attributed to the Zn:O4 coordination. Thus, it may be of medicinal relevance.

Keywords: Zinc(II), caffeic acid, complexation, structure-function relationship, diabetes, oxidative stress.

Graphical Abstract

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