In vitro and in silico pharmacological profiling of 3-(4,5-diaryl-1H-imidazol-2-yl)quinoline-2-amine hybrids
Nagarjuna Prakash Dalbanjan, Lokesh Bheemayya, Arihant Jayawant Kadapure, Manjunath P. Eelager, Thirukovela Madhava Swamy, Ravindra R. Kamble, S. K. Praveen Kumar
Abstract
Diabetes mellitus, characterized by impaired glucose metabolism, is a global health issue that necessitates the development of effective treatments. In this study, 4 3-(4,5-diaryl-1 H -imidazol-2-yl)quinoline-2-amine derivatives were evaluated in vitro and in silico for their potential antihyperglycemic, antioxidant, and anti-inflammatory activities[ (a)–(d) ]. The in vitro assays included α -amylase inhibition assay, glucose uptake assay (in yeast cells), antioxidant [2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) + radical scavenging, phosphomolybdenum assay], and albumin denaturation inhibition assay, which revealed that all compounds had significant bioactivities, with compound (a) having good potency for α -amylase inhibition (IC 50 = ∼111.60 μ g/mL), enhancing glucose uptake (IC 50 = ∼116.74 μ g/mL) while also exerting moderate antioxidant (IC 50 = 56–57 μ g/mL) and anti-inflammatory properties (IC 50 = ∼271 μ g/mL). Molecular docking studies confirmed strong interactions between the derivatives and target proteins α -amylase and peroxisome proliferator-activated receptor- γ , with compound (a) displaying favorable binding energies (−9.8 kcal/mol and −10.5 kcal/mol). In silico absorption, distribution, metabolism, excretion, and toxicity predictions using SwissADME and admetSAR 3.0 tools revealed that compound (a) has favorable drug-like properties such as high gastrointestinal absorption and moderate water solubility, whereas compounds (b), (c), and (d) had different bioavailability and toxicity profiles. The results of both in vitro and in silico studies indicate that the selected derivatives, particularly compound (a), have substantial pharmacological potential for managing hyperglycemia and associated oxidative stress and inflammation. Despite these promising findings, none of the tested compounds outperformed the efficacy of standard drugs in any of the in vitro assays, indicating the need for further structural modifications to enhance their therapeutic potential. The article highlights the integration of computational and experimental approaches to evaluate the pharmacological potential of quinoline-2-amine hybrids. The study provides insights into their antihyperglycemic, antioxidant, and anti-inflammatory properties, supporting their therapeutic potency.