Synthesis of Different Dipeptides From 4-Hydroxy Isoleucine and Evaluation of Their Anti-Diabetic Activity

Abstract

Introduction : Fenugreek is one of the oldest medicinal plants, originating in India and Northern Africa. The hypoglycemic effects of fenugreek have been attributed to several mechanisms. Under In vitro conditions, the amino acid 4-hydroxyisoleucine(4-OHIL) in fenugreek seeds increased glucose-induced insulin release in human and rat pancreatic islet cells. It was observed that 4-OHILextracted from fenugreek seeds has insulin tropic activity. This amino acid appeared to act only on pancreatic beta cells, since the levels of somatostatin and glucagon were not altered. Experimental: In order to separate amino acids from methanol extract of fenugreek seeds, ion exchange chromatography method containing 225H cationic resin was used. Five dipeptides were prepared from 4-OHILnamely; GLY-L-4-OHIL, ALA-L-4-OHIL, SER-L-4-OHIL, VAL-L-4-OHIL, THR-L-4-OHIL using cbZ-Cl in protecting step, DCC in peptide forming step and HBr in acetic acid in deprotection step. These five dipeptides are evaluated for invitro antidiabetic activity using non-enzymatic glycogenization heamoglobin assay method. Results: Five dipeptides were confirmed by spectral data like IR, MASS, NMR . Conclusion: In vitro antidiabetic studies showed that glycine l-4 hydroxy isoleucine showed improved activity compared to all other dipeptides and hence it is evaluated for invivo studies which showed remarkable anti diabetic activity compare to parent compound 4-hydroxy isoleucine.