2. Academic Validation
  3. Novel 4-quinoline-thiosemicarbazone derivatives: Synthesis, antiproliferative activity, in vitro and in silico biomacromolecule interaction studies and topoisomerase inhibition

Novel 4-quinoline-thiosemicarbazone derivatives: Synthesis, antiproliferative activity, in vitro and in silico biomacromolecule interaction studies and topoisomerase inhibition

  • Eur J Med Chem. 2019 Nov 15:182:111592. doi: 10.1016/j.ejmech.2019.111592.
Amélia Galdino Ribeiro 1,  Sinara Mônica Vitalino de Almeida 2,  Jamerson Ferreira de Oliveira 1,  Tulio Ricardo Couto de Lima Souza 3,  Keriolaine Lima Dos Santos 1,  Amanda Pinheiro de Barros Albuquerque 4,  Mariane Cajuba de Britto Lira Nogueira 5,  Luiz Bezerra de Carvalho Junior 6,  Ricardo Olímpio de Moura 7,  Aline Caroline da Silva 8,  Valéria Rêgo Alves Pereira 8,  Maria Carolina Accioly Brelaz de Castro 8,  Maria do Carmo Alves de Lima 1
Affiliations

Affiliations

  • 1 Laboratório de Química e Inovação Terapêutica (LQIT), Departamento de Antibióticos, Universidade Federal de Pernambuco, Recife, PE, 50670-901, Brazil.
  • 2 Laboratório de Immunopatologia Keizo Asami (LIKA), Universidade Federal de Pernambuco, Recife, PE, 50670-901, Brazil; Universidade de Pernambuco (UPE), Faculdade de Ciências, Educacão e Tecnologia de Garanhuns (FACETEG), Garanhuns, PE, 55290-000, Brazil. Electronic address: sinara.monica@upe.br.
  • 3 Unidade Acadêmica de Serra Talhada, Universidade Federal Rural de Pernambuco, Serra Talhada, PE, 56909-535, Brazil.
  • 4 Laboratório de Imunomodulação e Novas Abordagens Terapêuticas (LINAT), Universidade Federal de Pernambuco, Recife, PE, 50670-901, Brazil.
  • 5 Laboratório de Immunopatologia Keizo Asami (LIKA), Universidade Federal de Pernambuco, Recife, PE, 50670-901, Brazil; Centro Acadêmico de Vitória (CAV) - Universidade Federal de Pernambuco, Vitória de Santo Antão, PE, 55608-680, Brazil.
  • 6 Laboratório de Immunopatologia Keizo Asami (LIKA), Universidade Federal de Pernambuco, Recife, PE, 50670-901, Brazil.
  • 7 Departamento de Ciências Farmacêuticas, Centro de Ciências Biológicas e da Saúde, Universidade Estadual da Paraíba - Bodocongo, Campina Grande, PB, 58429-500, Brazil.
  • 8 Centro de Pesquisa Aggeu Magalhães (FIOCRUZ), Recife, PE, 50670-420, Brazil.
PMID: 31421632 DOI: 10.1016/j.ejmech.2019.111592
Abstract

Twelve 2-(quinolin-4-ylmethylene) hydrazinecarbothioamide derivatives were synthetized and their biological properties were investigated, among which, the ability to interact with DNA and BSA through UV-Vis absorption, fluorescence, Circular Dichroism, molecular docking and relative viscosity, antiproliferative activity against MCF-7 and T-47D mammary tumor cells and RAW-264.7 macrophages and inhibitory capacity of the enzyme Topoisomerase IIα. In the binding study with DNA and BSA, all the compounds displayed affinity for interaction with both biomolecules, especially JF-92 (p-ethyl-substituted), with binding constant of 1.62 × 106 and 1.43 × 105, respectively, and DNA binding mode by intercalation. The IC50 values were obtained between 0.81 and 1.48 μM and Topoisomerase inhibition results in 10 μM. Thus, we conclude that the reduction of the acridine to quinoline ring did not disrupt the antitumor action and that substitution patterns are important for biomolecule interaction affinity as they demonstrate the potential of these compounds for Anticancer therapy.

Keywords

BSA interaction; Breast cancer; DNA binding; Topoisomerase.

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