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 <...

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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:	2-amino-3-cyano-4<i>H</i>-chromenes cytotoxicity topoisomerase I antifungal activity CYP51 <i>Candida</i> spp. Medicine R Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/97b971ae3c79401fb4955520971950c1
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spelling	oai:doaj.org-article:97b971ae3c79401fb4955520971950c12021-11-25T18:39:25ZThree-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 Testing10.3390/ph141111101424-8247https://doaj.org/article/97b971ae3c79401fb4955520971950c12021-10-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1110https://doaj.org/toc/1424-8247Chromenes 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.Alberto FelicianoOmar Gómez-GarcíaCarlos H. EscalanteMario A. Rodríguez-HernándezMariana Vargas-FuentesDulce Andrade-PavónLourdes Villa-TanacaCecilio Álvarez-ToledanoMaría Teresa Ramírez-ApanMiguel A. VázquezJoaquín TamarizFrancisco DelgadoMDPI AGarticle2-amino-3-cyano-4<i>H</i>-chromenescytotoxicitytopoisomerase Iantifungal activityCYP51<i>Candida</i> spp.MedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1110, p 1110 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	2-amino-3-cyano-4<i>H</i>-chromenes cytotoxicity topoisomerase I antifungal activity CYP51 <i>Candida</i> spp. Medicine R Pharmacy and materia medica RS1-441
spellingShingle	2-amino-3-cyano-4<i>H</i>-chromenes cytotoxicity topoisomerase I antifungal activity CYP51 <i>Candida</i> spp. Medicine R Pharmacy and materia medica RS1-441 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 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
description	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.
format	article
author	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
author_facet	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
author_sort	Alberto Feliciano
title	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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/97b971ae3c79401fb4955520971950c1
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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

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