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

Yusuf Serdar Yazıcıoğlu; Şeydanur Elmas; Zeynep Kılıç; Murat Çelik; Buket Bakan; Ufuk Atmaca; Songül Bayrak

doi:10.1002/jbt.70261

journal article Open Access Apr 01, 2025

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

Yusuf Serdar Yazıcıoğlu Şeydanur Elmas Zeynep Kılıç Murat Çelik

Buket Bakan Ufuk Atmaca

Songül Bayrak

Journal of Biochemical and Molecular Toxicology Vol. 39 No. 4 · Wiley

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Abstract

ABSTRACTAn 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.

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Details

Published: Apr 01, 2025
Vol/Issue: 39(4)
License: View

Authors

Y

Yusuf Serdar Yazıcıoğlu

Department of Molecular Biology and Genetics, Faculty of Sciences Atatürk University Erzurum Turkey; Department of Chemistry, Faculty of Sciences Atatürk University Erzurum Turkey

�

Şeydanur Elmas

Department of Molecular Biology and Genetics, Faculty of Sciences Atatürk University Erzurum Turkey

Z

Zeynep Kılıç

Department of Molecular Biology and Genetics, Faculty of Sciences Atatürk University Erzurum Turkey; Department of Chemistry, Faculty of Sciences Atatürk University Erzurum Turkey

M

Murat Çelik

Department of Chemistry, Faculty of Sciences Atatürk University Erzurum Turkey

B

Buket Bakan

Department of Molecular Biology and Genetics, Faculty of Sciences Atatürk University Erzurum Turkey

U

Ufuk Atmaca

Department of Chemistry, Faculty of Sciences Atatürk University Erzurum Turkey

S

Songül Bayrak

Department of Chemistry, Faculty of Sciences Atatürk University Erzurum Turkey

Cite This Article

Yusuf Serdar Yazıcıoğlu, Şeydanur Elmas, Zeynep Kılıç, et al. (2025). Synthesis of Novel Isoindolinones: Carbonic Anhydrase Inhibition Profiles, Antioxidant Potential, Antimicrobial Effect, Cytotoxicity and Anticancer Activity. Journal of Biochemical and Molecular Toxicology, 39(4). https://doi.org/10.1002/jbt.70261

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

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