Isoindolinone Derivatives: Synthesis, In Vitro Anticancer, Antioxidant, and Molecular Docking Studies

Abstract In the present investigations, an efficient catalyst Cu(OTf) 2 was used for the synthesis of C(3)‐substituted isoindolinones ( 11a–h ) in a good to excellent yields. The structures of all compounds were characterized by FT‐IR, 1 H, 13 C NMR, and HRMS spectrometry techniques. Additionally, the single‐crystal structure of 2‐(2‐bromobenzyl)‐3‐hydroxyisoindolin‐1‐one (C₃₀H₂₄Br₂N₂O₄) 10e was elucidated by XRD analysis. Further, the anticancer activities of the synthesized compounds ( 10a–m ) and ( 11a–h ) were evaluated against two cancerous cell lines (A549 and MCF‐7) with two positive controls, such as doxorubicin and paclitaxel. In vitro results revealed that ferrocene‐substituted compound 11h proved to be a potential anticancer compound with IC 50 values of 1.0 and 1.5 µM against A549 and MCF‐7 cancerous cell lines, respectively. In addition, we report that the ferrocene‐substituted isoindolinone derivative 11h exhibited significant antioxidant activity by the reduced levels of 16.25% at 50 µg concentration. The compound 11h displayed promising antioxidant activity, which confirms that the ferrocene‐substituted isoindolinone has dual bioactive capabilities. Further, in silico molecular docking results indicated that the ferrocene‐substituted isoindolinone derivative 11h was efficiently binding to Bcl‐B protein with the estimated binding affinity of −6.7 kcal/mol. Altogether, our results suggest that the 11h shows promising anticancer and antioxidant activity.