Synthesis of Novel Isoindolinones: Carbonic Anhydrase Inhibition Profiles, Antioxidant Potential, Antimicrobial Effect, Cytotoxicity and Anticancer Activity

An efficient one-pot method has been developed for synthesizing novel isoindolinone derivatives from 2-benzoylbenzoic acid using chlorosulfonyl isocyanate and alcohols. This reaction occurs under mild, metal-free conditions, rendering it a sustainable and effective approach for isoindolinone synthesis. The inhibitory potential of the synthesized compounds against human carbonic anhydrase (hCA) I and II isozymes was evaluated and compared with the standard inhibitor, acetazolamide (AAZ). Additionally, their antimicrobial and antioxidant activities were assessed using various bioanalytical methods, with results benchmarked against standard reference compounds. Furthermore, cytotoxicity and anticancer activity were investigated in L929 and A549 cell lines via the WST-1 assay following a 24 h exposure. Among the synthesized derivatives, compounds 2c and 2f exhibited superior inhibitory effects on hCA I and II compared to AAZ, with Ki values ranging from 11.48 ± 4.18 to 16.09 ± 4.14 nM for hCA I and 9.32 ± 2.35 to 14.87 ± 3.25 nM for hCA II. These findings indicate that compounds 2c and 2f have a high affinity for the enzyme's active site, resulting in more effective inhibition of its catalytic activity. Compound 2e emerged as the most promising candidate, demonstrating potent carbonic anhydrase inhibition and significant antioxidant and antimicrobial properties. None of the synthesized compounds displayed cytotoxic effects on healthy cells at the tested concentrations. Additionally, compound 2a exhibited dose-dependent anticancer activity against A549 cells. These results suggest that isoindolinone derivatives, particularly 2f, hold substantial potential for further pharmaceutical development as multifunctional bioactive agents.