In vitro biological and in silico screening of novel iron(iii) complexes for DNA-targeted antitumor drug component

Two novel thiosemicarbazone-based iron(iii) complexes (Fe1 and Fe2) were synthesized and identified by analytical and spectroscopic methods. Their antiproliferative activity was investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) test against HT-29, HeLa, and L929 cell lines. The interaction between the complexes and calf thymus DNA were determined using electronic spectra and fluorescence spectra analysis. Gel electrophoresis was used to examine DNA cleavage and human topoisomerase-IIa inhibitory action. The complexes were screened for xanthine oxidase (XO) inhibitory activity and their antioxidant activities were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and phosphomolybdenum methods. In silico screening was performed to evince some pharmacological characteristics such as drug-likeness, bioactivity score and probable activity spectra of compounds (PASS) analysis using Molinspiration and PASS software. The iron(iii) complexes promoted the cleavage of DNA from the supercoiled form (Form I) to the nicked circular form (Form II), but did not create Form III, indicating single-stranded DNA cleavage. MTT results showed that Fe2 has more effective antiproliferative activity on HT-29 cells, Fe1 has more effective antiproliferative activity on HeLa cells, and the complexes generally moderately affect normal fibroblast L929 cells. The antiproliferation levels were consistent with the DNA interaction results. Both complexes had antioxidant activity and inhibited XO better than the standard drug allopurinol. In silico studies have shown that the iron(iii) complexes can have drug-like characteristics associated with remarkable pharmacokinetic properties that make sense of the experimental data regarding DNA-targeting, antioxidant, topoisomerase-IIa and XO inhibitory abilities.