Crystal Structure–Activity Relationship of Some MeO Phenylacrylonitriles: Dual Antimicrobial–Cytotoxic Effects and in Silico Perspectives

Methoxy-phenylacrylonitriles (2a–c) are synthesized and characterized by fourier-transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and X-ray crystallography (for 2a,b). Compound 2b shows selective cytotoxicity against MCF-7 cells (IC₅₀: 34 μM) and enhances activity against Gram-positive bacteria. Molecular docking reveals strong binding to CDK1/Cks2 (−9.5 kcal mol^{− 1}), supporting dual therapeutic potential.

Herein, methoxy-substituted phenylacrylonitrile derivatives 2(a–c) are synthesized via Knoevenagel condensation and characterized using fourier-transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and X-ray crystallography (for 2a and 2b). Although compounds 2a and 2b have previously been reported in terms of their structural features, their dual antimicrobial and anticancer activities, as well as crystallographic structure–activity relationships, have not yet been investigated. Notably, no earlier studies assessed their selective cytotoxicity using both cancerous (MCF-7) and healthy (L929) cell lines—a gap addressed in this work. Molecular docking analyzes reveal strong binding affinities to biological targets, including penicillin binding protein 2 (PBP2) (−8.4 kcal mol⁻¹ for 2c) and CDK1/Cks2 (−9.5 kcal mol⁻¹ for 2c), highlighting their dual-action potential. Antimicrobial assays against nine bacterial strains show minimum inhibitory concentration values ranging from 2.5 to 25 mg mL⁻¹, with 2c exhibiting notable activity against gram-positive bacteria. Cytotoxicity assays demonstrate potent effects against MCF-7 cells (IC₅₀: 34 μM for 2b, 44 μM for 2a), while 2c shows broader but moderate activity. The integration of crystallographic, docking, and biological assays underscores the therapeutic potential of these derivatives, with 2(a,b) emerging as selective candidates for breast cancer treatment.

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