Deciphering the cytotoxic and antioxidant potential of 3,5-disubstituted isoxazole-linked benzimidazolone derivatives

• Published in: Journal of molecular structure Vol. 1320; p. 139683
• Main Authors: Adardour, Mohamed, Drioua, Soufiane, Ait Lahcen, Marouane, Hdoufane, Ismail, Zaballos-García, Elena, Alanazi, Mohammed M., Doukkali, Anass, Chkirate, Karim, Cherqaoui, Driss, Mague, Joel T., Baouid, Abdesselam
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.01.2025
• Subjects: Antioxidant activity; Benzimidazolone; Cytotoxic; DFT; Isoxazole; Nitrile oxide; Isoxazole; Benzimidazolone; Nitrile oxide; DFT; Cytotoxic; Antioxidant activity
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.139683

•A series of 3,5-disubstituted Isoxazole-linked benzimidazolone derivatives was synthesized.•The synthesized isoxazoles were characterized using1H and 13C NMR, HRMS and single-crystal XRD.•All synthesized compounds were evaluated for their antioxidant activities and acute toxicity.•DFT calculations and Hirshfeld surface analysis were performed. A series of new isoxazole derivatives containing a benzimidazolone has been synthesized by cycloaddition reaction using various nitrile oxides. In all cases, these cycloadditions are completely chemo and regioselective. The structures of the new cycloadducts were characterized by 1H, 13C NMR spectroscopy, HRMS and confirmed in one case by a single crystal structure determination. The isoxazole compounds were evaluated for in vitro antioxidant activity using the DPPH and ABTS methods. As a result, compound 5a showed good antioxidant activity. The results of the acute toxicity study of the heterocycles studied by the oral route showed no deaths and no clinical signs of toxicity. Additionally, the Hirshfeld surface analysis and the molecular electrostatic potential using density functional theory (DFT) modeling at the B3LYP/6–31G(d,p) level. Hirshfeld surface analysis (dnorm surface and 2D-fingerprint plots) revealed the nature of intermolecular contacts. H⋯H interactions make the most significant contribution to crystal packing. The optimized structural parameters obtained through DFT calculations closely matched those determined via X-ray analysis, demonstrating strong agreement between theoretical predictions and experimental observations. [Display omitted]