Biological Evaluation of Novel Quinazolinone and Spiroquinazolinone Derivatives Synthesized via an Eco-Friendly Surfactant-Mediated Protocol

Abstract

A library of quinazolinone and spiroquinazolinone derivatives was synthesized through an environmentally benign multicomponent protocol using isatoic anhydride, primary amines, substituted benzaldehydes or isatin derivatives in aqueous medium in the presence of Triton X-100 as a surfactant catalyst. Fifteen compounds, comprising nine quinazolinones (4a–4i) and six spiroquinazolinones (6a–6f), were prepared in good to excellent yields and fully characterized by spectroscopic techniques. The synthesized molecules were evaluated for their antibacterial potential against three clinically relevant bacterial strains: Escherichia coli (ATCC 9637), Pseudomonas aeruginosa (ATCC BAA-427), and Staphylococcus aureus (ATCC 25923). Several derivatives displayed selective antibacterial activity. Compound 4b and compound 4i exhibited the most potent inhibition against S. aureus with IC₅₀ values of 1.56 μM, while compounds 4i and several spiro analogues (6a, 6b, 6d–6f) demonstrated moderate activity against E. coli with IC₅₀ values of 12.5 μM. None of the synthesized molecules showed significant activity against P. aeruginosa (IC₅₀ > 50 μM), indicating a marked strain selectivity. Preliminary structure–activity relationship analysis revealed that a para-methoxy substituent and incorporation of tyramine as the amine component were favorable for antibacterial activity.