Rational Design, Synthesis, Separation, and Characterization of New Spiroxindoles Combined with Benzimidazole Scaffold as an MDM2 Inhibitor

• DOI: 10.3390/separations10040225
• Publication Date: 2023-03-27T06:18:27Z
• Authors: Saeed Alshahrani; Abdullah Mohammed...; M. Ali; Abdullah Saleh Al...; Marwa M. Abu-Serie; Alexander Dömling; Muhammad Shafiq; Zaheer Ul-Haq; Assem Barakat
• Keywords: Benzimidazole; Microscale Thermophoresis; MTT assay; Docking (animal); Lead compound

Rational design for a new spiroxindoles, combined with benzimidazole scaffold to identify murine double minute two (MDM2) inhibitor was synthesized and characterized. The desired spiroxindoles were achieved via [3+2] cycloaddition reaction approach which afforded the cycloadducts four asymmetric centers separated in an excellent regioselective diastereoselective compound. subjected set of biochemical assays including NCI cell panel assay, MTT MDM2 binding analysis by microscale thermophoresis assay. anticancer reactivity tested compounds showed IC50 (µM) range between 3.797–6.879 µM, compound 7d = 3.797 ± 0.205 µM most active candidate series. results promising that identified 7a could be inhibited KD 2.38 μm. Compound developed network interactions receptor studied silico molecular docking.