RESUMEN
Three new and complementary approaches to S-arylation of 2-thiohydantoins have been developed: copper-catalyzed cross coupling with either arylboronic acids or aryl iodides under mild conditions, or direct nucleophilic substitution in activated aryl halides. For 38 diverse compounds, reaction yields for all three methods have been determined. Selected by molecular docking, they have been tested on androgen receptor activation, and p53-Mdm2 regulation, and A549, MCF7, VA13, HEK293T, PC3, LnCAP cell lines for cytotoxicity, Two of them turned out to be promising as androgen receptor activators (likely by allosteric regulation), and another one is shown to activate the p53 cascade. It is hoped that 2-thiohydantoin S-arylidenes are worth further studies as biologically active compounds.
Asunto(s)
Andrógenos/química , Andrógenos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Tiohidantoínas/química , Tiohidantoínas/farmacología , Regulación Alostérica/efectos de los fármacos , Andrógenos/síntesis química , Antineoplásicos/síntesis química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Técnicas de Química Sintética , Células HEK293 , Humanos , Simulación del Acoplamiento Molecular , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Mapas de Interacción de Proteínas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Receptores Androgénicos/metabolismo , Tiohidantoínas/síntesis química , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
NiBr2 reacts with 3-hexyne in the presence of Mg and EtOH to give the cyclobutadiene bromide complex [(C4Et4)NiBr2]2, which serves as a general precursor for various cyclobutadiene nickel compounds. In particular, complexes with 2-electron ligands (C4Et4)Ni(L)Br2 (L = PPh3, P(OMe)3, pyridine), complexes with bidentate ligands [(C4Et4)Ni(L2)Br]PF6 (L2 = bipyridine, phenanthroline), and nickelacarborane (C4Et4)NiC2B9H11 were obtained from [(C4Et4)NiBr2]2 in 70-95% yields. The reactions of [(C4Et4)NiBr2]2 with an excess of strong ligands, such as tBuNC or dppe, led to the displacement of cyclobutadiene. The structures of the five compounds have been established by X-ray diffraction analysis. The previously reported data on cyclobutadiene nickel complexes have been also reviewed.
RESUMEN
The modification of Chan-Lam-Evans cross-coupling reaction for the selective Se-arylation of 2-selenohydantoins under base-free mild conditions via aryl boronic acids is described herein. This approach was used to synthesize novel 5-arylidene-3-substituted-2-(arylselanyl)-imidazoline-4-ones with high yields. The anticancer activity of the final compounds was evaluated in vitro against different cancer cells, and thus, the possibility of 5-arylidene-3-substituted-2-(arylselanyl)-imidazoline-4-ones successful application as cytotoxic agents was demonstrated.
