Topoisomerase inhibition and albumin interaction studies of acridine-thiosemicarbazone derivatives.

Topoisomerase inhibition and albumin interaction studies of acridine-thiosemicarbazone derivatives.
Int J Biol Macromol. 2019 Jul 16;:
Authors: da Silva Filho FA, de Freitas Souza T, Ribeiro AG, Alves JEF, de Oliveira JF, de Lima Souza TRC, de Moura RO, do Carmo Alves de Lima M, de Carvalho Junior LB, de Almeida SMV
Abstract
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.
PMID: 31323270 [PubMed - as supplied by publisher]

Source: International Journal of Biological Macromolecules - July 15, 2019 Category: Biochemistry Authors: da Silva Filho FA, de Freitas Souza T, Ribeiro AG, Alves JEF, de Oliveira JF, de Lima Souza TRC, de Moura RO, do Carmo Alves de Lima M, de Carvalho Junior LB, de Almeida SMV Tags: Int J Biol Macromol Source Type: research