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Topoisomerase inhibition and albumin interaction studies of acridine-thiosemicarbazone derivatives

2019; Elsevier BV; Volume: 138; Linguagem: Inglês

10.1016/j.ijbiomac.2019.07.097

1879-0003

Francivaldo Araújo da Silva Filho, Thaís de Souza, Amélia Galdino Ribeiro, Josival Emanuel Ferreira Alves, Jamerson Ferreira de Oliveira, Túlio Ricardo Couto de Lima Souza, Ricardo Olímpio de Moura, Maria do Carmo Alves de Lima, Luiz Bezerra de Carvalho, Sinara Mônica Vitalino de Almeida,

Synthesis and biological activity

In the present study, acridine-thiosemicarbazones (ATD) derivatives were tested for their interaction properties with BSA through UV-Vis absorption and fluorescence spectroscopic studies. Both hyperchromic and hypochromic effects, as well as red or blue shifts were demonstrated after the derivatives were added to the BSA. Values for the binding constant (Kb) ranged from 1.62 × 104 to 8.71 × 105 M-1 and quenching constant (KSV) from 3.46 × 102 to 7.83 × 103 M-1 indicating a good affinity to BSA protein. Complementary, two compounds were selected to assess their inhibition activity against topoisomerase IIα enzyme, of which derivative 3a presented the best result. Moreover, to evaluate protein-ligand interactions, as well as the antitopoisomerase potential of these compounds, tests of molecular modeling were performed between all compounds using the albumin and Topoisomerase IIα/DNA complex. Finally, in silico studies showed that all derivatives used in this research displayed good oral bioavailability potential.