Semi-synthesis of β-keto-1,2,3-triazole derivatives from ethinylestradiol and evaluation of the cytotoxic activity

Thayane M Queiroz; Erika V M Orozco; Valdenizia R Silva; Luciano S Santos; Milena B P Soares; Daniel P Bezerra; André L M Porto

doi:10.1016/j.heliyon.2019.e02408

Semi-synthesis of β-keto-1,2,3-triazole derivatives from ethinylestradiol and evaluation of the cytotoxic activity

Heliyon. 2019 Sep 6;5(9):e02408. doi: 10.1016/j.heliyon.2019.e02408. eCollection 2019 Sep.

Authors

Thayane M Queiroz¹, Erika V M Orozco¹, Valdenizia R Silva², Luciano S Santos², Milena B P Soares², Daniel P Bezerra², André L M Porto¹

Affiliations

¹ Laboratório de Química Orgânica e Biocatálise, Instituto de Química de São Carlos, Universidade de São Paulo, Av. João Dagnone, 1100, Ed. Química Ambiental, Santa Angelina, São Carlos, SP, 13563-120, Brazil.
² Fundação Oswaldo Cruz, Centro de Pesquisa Gonçalo Moniz, R. Waldemar Falcão, 121, Candeal, Salvador, BA, 40296-710, Brazil.

Abstract

In this study, we report our contribution to the application of the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction for the synthesis of β-keto-1,2,3-triazole derivatives 3a-f from ethinylestradiol and their application in the inhibition of two human cancer cells lines: human breast adenocarcinoma (MCF-7) and human hepatocellular carcinoma (HepG2). The β-keto-1,2,3-triazole derivates 3a-f exhibited moderate cytotoxic activity for the HepG2 cells with IC₅₀ values of 29.7 μM (3a), 16.4 μM (3b), 17.8 μM (3c), 20.4 μM (3d), 28.1 μM (3e) and 28.2 μM (3f). The semi-synthetic β-keto-1,2,3-triazoles derivatives 3a-f were all characterized by FT-IR, NMR, HRMS and [α]_D.

Keywords: Breast adenocarcinoma; Click reaction; Ethinylestradiol; Hepatocellular carcinoma; Organic chemistry; Pharmaceutical chemistry; Toxicology; β-keto-1,2,3-triazoles.