Ultrasound-Assisted Synthesis of Isonicotinamide Derivatives Catalyzed by Biogenic ZrNPs and Their Biological Evaluation

Abstract

In this study, we describe a one-pot, three-component synthesis method for creating N-(7-R)-2-oxa-6-azabicyclo[3.2.0]heptan-6-yl)isonicotinamide derivatives (4a–g). This method involves the condensation of isoniazid (1) with various aromatic aldehydes (2a–g), followed by a 2π+2π cycloaddition with 2,3-dihydrofuran (3), using zinc nanoparticles (ZrNPs) as an environmentally friendly, efficient, and recyclable catalyst under ultrasonic irradiation. The synthesized derivatives (4a–g) were characterized using ¹H NMR, ¹³C NMR, FTIR, and other spectroscopic techniques. These compounds exhibited good to excellent antibacterial activity against Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922), but showed no significant activity against Pseudomonas aeruginosa (ATCC 27853). Additionally, they demonstrated good to excellent antifungal activity against Candida species, as well as promising antitubercular activity against Mycobacterium tuberculosis strains. The ZrNPs used in the reaction were synthesized by reducing zirconium ions using extracts from the Sphingobium sp. plant leaves under ultrasonic irradiation. The formation of ZrNPs was confirmed by XRD, UV–Vis, FESEM, TEM, and FTIR analyses. Furthermore, the ZrNPs themselves exhibited notable antifungal, antitubercular, and antimalarial activity.