RESUMEN
A series of new diethyl(alkyl/aryl/heteroarylamino)(4-(pyridine-2-yl)phenyl)methylphosphonates (4a-t) were synthesized via three-component Kabachnik-Field's reaction of 4-(pyridin-2-yl)benzaldehyde, diethylphosphite and various primary amines, catalyzed by cupric acetate monohydrate [Cu(OAc)(2) â H(2)O] under solvent-free and microwave irradiation conditions. Their computational docking analysis supported them as good therapeutic agents to the breast cancer aromatase enzyme and ascertained 4a, 4h, 4m, 4n, and 4t as potential molecules with good binding affinities varying from -9.0 to -9.6 kcal/mol and containing the 4-(pyridine-2-yl)phenyl moiety as a pharmacophore. Their in vitro screening performed for the anti-cell proliferation activity against MBC-MCF7 cells by MTT and Trypan blue assays confirmed 4m, 4n, and 4q as promising compounds to sustain a low percentage of cell viability at 20 µg/mL concentration. These compounds were also evaluated for their antioxidant activity by the DPPH method and the results established that compounds 4m, 4n, and 4q show around 10% higher activity than the standard antioxidant ascorbic acid.
Asunto(s)
Antineoplásicos/farmacología , Antioxidantes/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Organofosfonatos/farmacología , Antineoplásicos/química , Antioxidantes/síntesis química , Antioxidantes/química , Ácido Ascórbico/farmacología , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Femenino , Humanos , Células MCF-7 , Simulación del Acoplamiento Molecular , Organofosfonatos/síntesis química , Organofosfonatos/química , Relación Estructura-ActividadRESUMEN
A simple and efficient one pot synthesis of 2-amino-4H-chromen-4-yl phosphonate derivatives has been accomplished by the condensation of salicylaldehyde, malononitrile/ethylcyanoacetate and triethyl phosphite/trimethyl phosphite in the presence of molecular iodine as catalyst in water at room temperature. All the reactions were very clean and the products were obtained in very good to excellent yields. The title compounds are characterized by IR, 1H-, 13C-, 31P-NMR and mass spectra, also studied their antimicrobial and antioxidant activity.