Structure-activity relationship and molecular docking insights into newly synthesized Quinoline derivatives

Abstract

Quinoline derivatives received much interest for the development of antidiabetic drugs because of to their diverse biological activities and structural flexibility. In this work, a novel series of quinoline based compounds were synthesised and characterised by different spectroscopic techniques. The structural modifications were purposefully done to evaluate their structure-activity relationship (SAR) in order to improve their antidiabetic action. We done molecular docking analyses of the main antidiabetic targets, which were α-glucosidase, to study the binding and interaction of them with other. Inhibition of alpha-glycosidase, a major therapeutic target for the treatment of type 2 diabetes, is an efficient approach to reduce postprandial hyperglycaemia by enhancing the digestion of carbohydrates in the small intestine. Docking studies revealed significant binding interactions of several drugs with key amino acid residues of the active sites, indicating significant inhibitory potential. The structure-activity relationship analysis revealed that substitutions at key positions of the quinoline ring significantly influenced the binding affinity and orientation within the target proteins. Moreover, in silico ADMET and drug-likeness investigations showed that the most active derivatives have good pharmacokinetic properties and low projected toxicity. The results indicate the possibility of quinoline based structure in the development of new antidiabetic medicines and provide a strong basis for further in vitro and in vivo studies. Keywords: Quinoline, SAR, ADME, type 2 diabetes, Docking study