Synthesis of functionalized benzofuran esters through Suzuki-Miyaura cross-coupling reactions, their DFT and pharmacological studies.

Abstract

The Suzuki-Miyaura cross-coupling reaction was used to synthesize phenylbenzofuran-2-carboxylate derivatives (4a- 4f). The structural features of the target molecules were analyzed using two computational tools, e.g., molecular docking and DFT studies. Based on computational studies, target molecules were further screened for hemolytic and enzyme inhibitory activity, e.g., anti-urease and α-glucosidase, investigated to evaluate their biological potential. Hemolytic assay findings indicate that synthesized molecules 4a-4f are non-toxic to RBCs, while Compound (4d) and (4a) showed excellent anti-urease and α-glucosidase inhibitory activity (IC₅₀ =13.38 ±1.75µM and (IC₅₀ = 60.5 ±1.53 µM). comparable to standard drugs. DFT and molecular docking predictions of structural features supported the experimental results. Most and least reactive molecules in this series (4a-4f) are identified by comparing energies (ΔE). 4f exhibits the lowest ∆E of 3.20 eV, indicating its least stability in the synthesized series (4a-4f). In contrast, 4b displays the highest ∆E gap of 6.42 eV, suggesting its highest stability and least reactivity. In this work, computational and in vitro methodologies provided complimentary insights for effective molecular screening of drug candidates, specifically in terms of binding affinity and toxicity profiles.