Open AccessDiacetate Naphthoquinone Derivatives Tethered to 1,2,3-Triazoles: Synthesis and Cytotoxicity Evaluation in Caco-2 Cells
Author(s) -
Dora C. S. Costa,
Adriane Francisco,
Beatriz Matuck,
Priscila de Souza Furtado,
Alana de Oliveira,
Vitor WonHeld Rabelo,
P.C Sathler,
Paula Alvarez Abreu,
Vı́tor F. Ferreira,
Luiz Cláudio da Silva,
Fernando de Carvalho da Silva
Publication year - 2022
Publication title -
journal of the brazilian chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.337
H-Index - 70
eISSN - 1678-4790
pISSN - 0103-5053
DOI - 10.21577/0103-5053.20210123
Subject(s) - chemistry , naphthoquinone , ceric ammonium nitrate , cycloaddition , prodrug , acetic anhydride , combinatorial chemistry , cytotoxicity , 1,4 naphthoquinone , selectivity , organic chemistry , stereochemistry , biochemistry , in vitro , polymer , grafting , catalysis
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.