The effect of O-alkylated chain length on in-vitro anti-hyperglycemic and anti-obesity activity of garcinol derivatives

Abstract

Type 2 Diabetic Mellitus has become one of the major global health issue, while obesity being a major risk factor for its development. Natural product and their semi-synthetic derivatives have shown promising therapeutic potential, with fewer side effects compared to synthetic drugs. Garcinol is one such potent anti-hyperglycemic and anti-obesity secondary metabolite rich in genus Garcinia. However, there have been no reported studies on its semi-synthetic analogs. Hence, the present study was aimed to synthesize O-alkylated derivatives and evaluate the effect of the alkyl chain length on its in-vitro anti-hyperglycemic and anti-obesity properties. Garcinol was isolated from the acetone-water (9:1) extract of dried fruit rinds of Garcinia quaesita and characterized by spectroscopic methods and melting point data. Three novel O-alkylated derivatives of garcinol were synthesized using RX (C2H5I (Product 1), C3H7Br (Product 2), C6H13Br (Product 3)) and a mild base; K2CO3(acetone). The products were characterized by spectroscopic data (Mass, NMR and FTIR). The in-vitro anti-hyperglycemic activity was assessed by α-amylase and α-glucosidase enzyme inhibition assays while, the anti-obesity activity was evaluated by pancreatic lipase enzyme inhibition assay. Product 1 showed no significance difference (p > 0.05) in α-amylase (IC50 28.45 ± 1.17 mg L-1) and α-glucosidase (IC50 12.48 ± 0.28 mg L-1) inhibitory potential while Product 2 and Product 3 showed significantly lower (p < 0.05) α-amylase and α-glucosidase inhibitory activity compared to garcinol (α-amylase; IC50 37.81 ± 1.48 mg L-1 and α- glucosidase; IC50 17.18 ± 1.53 mg L-1). Product 1 (IC50 53.36 ± 1.23 mg L-1) showed significantly lower (p < 0.05) pancreatic lipase inhibitory potential while product 2 (IC50 31.75 ± 0.32 mg L-1) showed no significant difference (p>0.05) in pancreatic lipase inhibitory activity compared to garcinol (IC50 38.93 ± 0.63 mg L-1). Further, the Product 3 (IC50 27.13 ± 1.62 mg L-1) exhibited significantly higher (p < 0.05) pancreatic lipase inhibitory potential compared to garcinol (IC50 38.93 ± 0.63 mg L-1). Based on this study, it can be concluded that O-alkylated chain length has positive effect on anti-obesity potential, and a negative impact on anti-hyperglycemic potential. However, future studies are required to confirm this trend with more examples.