Interaction study with DNA/HSA, anti-topoisomerase IIα, cytotoxicity and in vitro antiproliferative evaluations and molecular docking of indole-thiosemicarbazone compounds.

Autor: Jacob IT; Department of Antibiotics, Federal University of Pernambuco, 50670-901, Brazil., da Cruz Filho IJ; Department of Antibiotics, Federal University of Pernambuco, 50670-901, Brazil., Alves JEF; Laboratório de Imunopatologia Keizo Asami (LIKA), Universidade Federal de Pernambuco, 50670-901, Brazil., de Melo Souza F; Universidade de Pernambuco (UPE), Multicampi Garanhuns, Garanhuns, PE 55290-000, Brazil., de Azevedo RDS; Universidade de Pernambuco (UPE), Multicampi Garanhuns, Garanhuns, PE 55290-000, Brazil., Marques DSC; Department of Antibiotics, Federal University of Pernambuco, 50670-901, Brazil., de Lima Souza TRC; Rural University of Pernambuco, Academic Unit of Belo Jardim, 55156-580 Belo Jardim, PE, Brazil., Dos Santos KL; Department of Antibiotics, Federal University of Pernambuco, 50670-901, Brazil., da Rocha Pitta MG; Department of Biochemistry, Federal University of Pernambuco, 50670-901, Brazil., de Melo Rêgo MJB; Department of Biochemistry, Federal University of Pernambuco, 50670-901, Brazil., Oliveira JF; University for the International Integration of Afro-Brazilian Lusophony (UNILAB), 62790-970 Redenção, CE, Brazil., Almeida SMV; Laboratório de Imunopatologia Keizo Asami (LIKA), Universidade Federal de Pernambuco, 50670-901, Brazil; Universidade de Pernambuco (UPE), Multicampi Garanhuns, Garanhuns, PE 55290-000, Brazil. Electronic address: sinara.monica@upe.br., do Carmo Alves de Lima M; Department of Antibiotics, Federal University of Pernambuco, 50670-901, Brazil.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2023 Apr 15; Vol. 234, pp. 123606. Date of Electronic Publication: 2023 Feb 10.
DOI: 10.1016/j.ijbiomac.2023.123606
Abstrakt: In this work we will discuss the antiproliferative evaluation and the possible mechanisms of action of indole-thiosemicarbazone compounds LTs with anti-inflammatory activity, previously described in the literature. In this perspective, some analyzes were carried out, such as the study of binding to human serum albumin (HSA) and to biological targets: DNA and human topoisomerase IIα (topo). Antiproliferative study was performed with DU-145, Jukart, MCF-7 and T-47D tumor lines and J774A.1, besides HepG2 macrophages and hemolytic activity. In the HSA interaction tests, the highest binding constant was 3.70 × 10 6  M -1 , referring to LT89 and in the fluorescence, most compounds, except for LT76 and LT87, promoted fluorescent suppression with the largest Stern-Volmer constant for the LT88 3.55 × 10 4 . In the antiproliferative assay with DU-145 and Jurkat strains, compounds LT76 (0.98 ± 0.10/1.23 ± 0.32 μM), LT77 (0.94 ± 0.05/1.18 ± 0.08 μM) and LT87 (0.94 ± 0.12/0.84 ± 0.09 μM) stood out, due to their IC 50 values mentioned above. With the MCF-7 and T-47D cell lines, the lowest IC 50 was presented by LT81 with values of 0.74 ± 0.12 μM and 0.68 ± 0.10 μM, respectively, followed by the compounds LT76 and LT87. As well as the positive control amsacrine, the compounds LT76, LT81 and LT87 were able to inhibit the enzymatic action of human Topoisomerase IIα.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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