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

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 II alpha (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 x 106 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 x 104. In the antiproliferative assay with DU-145 and Jurkat strains, compounds LT76 (0.98 +/- 0.10/1.23 +/- 0.32 mu M), LT77 (0.94 +/- 0.05/1.18 +/- 0.08 mu M) and LT87 (0.94 +/- 0.12/ 0.84 +/- 0.09 mu M) stood out, due to their IC50 values mentioned above. With the MCF-7 and T-47D cell lines, the lowest IC50 was presented by LT81 with values of 0.74 +/- 0.12 mu M and 0.68 +/- 0.10 mu M, 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 II alpha.

Automated summary

This work evaluates the antiproliferative effects and possible mechanisms of indole-thiosemicarbazone compounds LTs with anti-inflammatory activity. The compounds were studied for their binding to HSA, DNA, and human topo, and their fluorescence properties were also analyzed. LT89 exhibited the highest binding constant to HSA, while most compounds showed fluorescent suppression, with LT88 having the highest Stern-Volmer constant. LT76, LT77, and LT87 showed significant antiproliferative effects on DU-145 and Jurkat cells, and LT81 showed the lowest IC50 values on MCF-7 and T-47D cells. Additionally, compounds LT76, LT81, and LT87 inhibited the enzymatic action of human topo II alpha, similar to the positive control amsacrine.