Title
Novel 4-quinoline-thiosemicarbazone derivatives: Synthesis, antiproliferative activity, in vitro and in silico biomacromolecule interaction studies and topoisomerase inhibition
Author
Amélia Galdino Ribeiro, Sinara Mônica Vitalino de Almeida, Jamerson Ferreirade Oliveira, Tulio Ricardo Couto de Lima Souza, Keriolaine Lima dos Santos, Amanda Pinheiro de Barros Albuquerque, Mariane Cajuba de Britto Lira Nogueira, Luiz Bezerra de Carvalho Junior, Ricardo Olímpio de Moura, Aline Carolineda Silva, Valéria Rêgo Alves Pereira, Maria Carolina Accioly Brelaz de Castro, Maria do Carmo Alves de Lima
Year
2019
Journal
European Journal of Medicinal Chemistry
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.
Instrument
FP-6300, J-815
Keywords
Circular dichroism, Fluorescence, Secondary structure, Protein structure, DNA binding, Biochemistry, Organic chemistry, Medicinal