Ecofriendly Synthesis, Biological Evaluation, and Molecular Docking Studies of a Novel N-[3-(Benzo[d][1,3]dioxol-5-yl]-1,8-naphthyridine Benzamide Derivatives and Phenyl-triazolo-[1,8]naphthyridine Scaffolds

Abstract

An efficient and rapid synthetic method was developed for the construction of N-(1,8-naphthyridin-2-yl)benzamides and 9-aryl-[1,2,4]triazolo[4,3-a][1,8]naphthyridine derivatives via microwave irradiation, obtained in excellent yields. This approach offers significant advantages, including reduced reaction time, enhanced yields, improved product purity, minimal by-product formation, and low energy consumption. The synthesized compounds were evaluated for their in vitro antimicrobial activity against pathogenic strains, revealing remarkable activity for certain derivatives compared to standard clinical drugs. Among them 6-(benzo[d][1,3]dioxol-5-yl)-9-(4-fluorophenyl)-[1,2,4]triazolo[4,3-a][1,8]naphthyridine exhibited the highest antimicrobial activity among the series. In addition, molecular docking studies further supported the experimental findings, demonstrating strong binding affinities of the active compounds to the target protein via hydrogen bonding interactions. These interactions suggest the synthesized compounds exhibit a stable and effective binding mode, correlating with their observed antimicrobial properties.