Three-Component Synthesis of 2-Amino-3-cyano-4<i>H</i>-chromenes, In Silico Analysis of Their Pharmacological Profile, and In Vitro Anticancer and Antifungal Testing

Chromenes are compounds that may be useful for inhibiting topoisomerase and cytochrome, enzymes involved in the growth of cancer and fungal cells, respectively. The aim of this study was to synthesize a series of some novel 2-amino-3-cyano-4-aryl-6,7-methylendioxy-4<i>H</i>-chromenes <...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Alberto Feliciano, Omar Gómez-García, Carlos H. Escalante, Mario A. Rodríguez-Hernández, Mariana Vargas-Fuentes, Dulce Andrade-Pavón, Lourdes Villa-Tanaca, Cecilio Álvarez-Toledano, María Teresa Ramírez-Apan, Miguel A. Vázquez, Joaquín Tamariz, Francisco Delgado
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
Materias:
R
Acceso en línea:https://doaj.org/article/97b971ae3c79401fb4955520971950c1
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Descripción
Sumario:Chromenes are compounds that may be useful for inhibiting topoisomerase and cytochrome, enzymes involved in the growth of cancer and fungal cells, respectively. The aim of this study was to synthesize a series of some novel 2-amino-3-cyano-4-aryl-6,7-methylendioxy-4<i>H</i>-chromenes <b>4a–o</b> and 2-amino-3-cyano-5,7-dimethoxy-4-aryl-4<i>H</i>-chromenes <b>6a–h</b> by a three-component reaction, and test these derivatives for anticancer and antifungal activity. Compounds <b>4a</b> and <b>4b</b> were more active than cisplatin (<b>9</b>) and topotecan (<b>7</b>) in SK-LU-1 cells, and more active than <b>9</b> in PC-3 cells. An evaluation was also made of the series of compounds <b>4</b> and <b>6</b> as potential antifungal agents against six <i>Candida</i> strains, finding their MIC<sub>50</sub> to be less than or equal to that of fluconazole (<b>8</b>). Molecular docking studies are herein reported, for the interaction of <b>4</b> and <b>6</b> with topoisomerase IB and the active site of CYP51 of <i>Candida</i> spp. Compounds <b>4a–o</b> and <b>6a–h</b> interacted in a similar way as <b>7</b> with key amino acids of the active site of topoisomerase IB and showed better binding energy than <b>8</b> at the active site of CYP51. Hence, <b>4a–o</b> and <b>6a–h</b> are good candidates for further research, having demonstrated their dual inhibition of enzymes that participate in the growth of cancer and fungal cells.