Synthesis and molecular docking of novel biguanide-NSAIDs hybrid with dual anti-diabetic and anti-inflammatory activity

Abstract

Herein, we report the synthesis, characterization, anti-diabetic and anti-inflammatory activities of biguanide hybridized with NSAIDS drugs linked via hydrazide. Diabetes Mellitus is a chronic metabolic condition that can lead to significant complications and a high fatality rate worldwide. Efforts are ramping up to find and develop novel α-glucosidase and α-amylase inhibitors that are both effective and potentially safe. Docking studies have also been done for antidiabetic target. The molecular docking results displayed that the constituents strongly bind α-amylase and α-glucosidase while achieving better binding affinities. IBU (182.64 μg/mL and 65.41 μg/mL), NAP (195.25 μg/mL and 78.53 μg/mL) and DIC (185.94 μg/mL and 91.26 μg/mL) showed a better antidiabetic activity with α-glucosidase and α-amylase respectively. Also, IBU and KET showed a better reduction in paw volume 0.710 mL and 0.718 mL at 240 min indicating better anti-inflammatory effect. ADMET study states, lipophilicity of the compounds, reflected in their log Po/w values, varies significantly. ASP (3c) is quite hydrophilic, while DIC (3e) and FLU (3 g) are more lipophilic. Among the all-synthesized biguanide compounds ASP and KET exhibits low gastrointestinal absorption. MEF showed high skin permeation and ASP showed low skin permeation. From all the studies it concludes that the synthesised biguanide derivatives could be a potential in treatment of various inflammatory conditions associated with Diabetes Mellitus.