Diacetate Naphthoquinone Derivatives Tethered to 1,2,3-Triazoles: Synthesis and Cytotoxicity Evaluation in Caco-2 Cells

• Main Author: Costa,Dora C. S.
• Publication Date: 2022
• Other Authors: Francisco,Adriane S., Matuck,Beatriz V. A., Furtado,Priscila S., Oliveira,Alana A. S. C. de, Rabelo,Vitor W.-H., Sathler,Plínio C., Abreu,Paula A., Ferreira,Vitor F., Silva,Luiz Cláudio R. P. da, Silva,Fernando C. da
• Format: Article
• Language: eng
• Source: Journal of the Brazilian Chemical Society (Online)
• Download full: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532022000100048
• topic: naphthoquinones; lapachones; cancer; human epithelial colorectal adenocarcinoma cells; molecular docking; topoisomerase

Acetylated compounds prepared from naphthoquinones have been reported as antitumoral prodrugs. Exploring the synthetic versatility of the naphthoquinone and triazolic nuclei, herein we report a simple and efficient synthetic route to prepare a series of sixteen prodrugs prototype of 1,2,3-triazoles-naphthoquinodoic acetyl derivatives. The compounds 10a-10h and 11a-11h were obtained by oxidative cycloaddition reaction between lawsone and 4-vinyl-1H-1,2,3-triazoles promoted by ceric ammonium nitrate (CAN) in alkaline medium followed by reductive acetylation of the quinones in excess of metallic zinc and acetic anhydride in yields up to > 98%. All derivatives revealed to be hemocompatible and the compound 11e exhibited the most promising profile against Caco-2 cells showing the higher selectivity index. Molecular docking suggests that these compounds could exert their cytotoxic activity through inhibition of one topoisomerase II isoform, at least.