2. Academic Validation
  3. Synthesis of thiophene-thiosemicarbazone derivatives and evaluation of their in vitro and in vivo antitumor activities

Synthesis of thiophene-thiosemicarbazone derivatives and evaluation of their in vitro and in vivo antitumor activities

  • Eur J Med Chem. 2015 Nov 2:104:148-56. doi: 10.1016/j.ejmech.2015.09.036.
Jamerson Ferreira de Oliveira 1,  Anekécia Lauro da Silva 1,  Débora Barbosa Vendramini-Costa 2,  Cezar Augusto da Cruz Amorim 1,  Júlia Furtado Campos 3,  Amélia Galdino Ribeiro 1,  Ricardo Olímpio de Moura 4,  Jorge Luiz Neves 5,  Ana Lúcia Tasca Gois Ruiz 2,  João Ernesto de Carvalho 2,  Maria do Carmo Alves de Lima 6
Affiliations

Affiliations

  • 1 Universidade Federal de Pernambuco (UFPE), Departamento de Antibióticos, 50670-901 Recife, PE, Brazil.
  • 2 Universidade Estadual de Campinas (Unicamp), Divisão de Farmacologia e Toxicologia, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), 13083-970 Campinas, SP, Brazil.
  • 3 Instituto Nacional de Tecnologia Nordeste/MCT, Centro de Tecnologias Estratégicas do Nordeste, 50740-540 Recife, PE, Brazil.
  • 4 Universidade Estadual da Paraíba (UEPB), Departamento de Farmácia, 58429-500 Paraíba, PB, Brazil.
  • 5 Universidade Federal de Pernambuco (UFPE), Departamento de Química Fundamental, 50670-901 Recife, PE, Brazil.
  • 6 Universidade Federal de Pernambuco (UFPE), Departamento de Antibióticos, 50670-901 Recife, PE, Brazil. Electronic address: nenalima.mariadocarmo@gmail.com.
PMID: 26454648 DOI: 10.1016/j.ejmech.2015.09.036
Abstract

A series of thiophene-2-thiosemicarbazones derivatives (5-14) was synthesized, characterized and evaluated for their antitumor activity. They were tested in vitro against human tumor cell lines through the colorimetric method. The results revealed that compounds 7 and 9 were the most effective in inhibiting 50% of the cell growth after 48 h of treatment. As compound 7 showed a potent antiproliferative profile, it has been chosen for further studies in 786-0 cell line by flow cytometry. Treatments with compound 7 (50 μM) induced early phosphatidylserine exposure after 18 h of exposure and this process progressed phosphatidylserine exposure with loss of cell membrane integrity after 24 h of treatment, suggesting a time-dependent cell death process. Regarding the cell cycle profile, no changes were observed after treatment with compound 7 (25 μM), suggesting a mechanism of cell death independent on the cell cycle. The in vivo studies show that compound 7 possess low acute toxicity, being the doses of 30-300 mgKg(-1) chosen for studies in Ehrlich solid tumor model in mice. All doses were able to inhibit tumor development being the lowest one the most effective. Our findings highlight thiophene-2-thiosemicarbazones as a promising class of compounds for further studies concerning new Anticancer therapies.

Keywords

Antitumor; Cytotoxicity; Medicinal chemistry; Thiophene; Thiosemicarbazone.

Figures