In-vitro antiproliferative evaluation of newly synthesized titanium(IV) metallacyclic complexes on HeLa and MCF7 cell lines

Abstract

Abstract A series of eight metalacyclic derivatives of titanium i.e. [ (acac)Ti(ph)L ] ( TiC1–TiC7 ) and [ LTiL ] ( TiC8 ) (where acacH = acetylacetone, ph = phenol derivatives and L = ligand L1) were synthesized in anhydrous media and were characterized employing NMR ( 1 H and 13 C), UV-Vis, FT-IR and ESI-mass analyses. Viscosity assays, absorption and fluorescence spectroscopy and molecular docking studies have been extrapolated to investigate the complexes’ interaction with CT-DNA and bovine serum albumin (BSA). Interaction of the complexes with CT-DNA was validated as groove binding mode using UV-Vis absorption spectra as evidenced by their intrinsic binding constants of all wherein TiC1 and TiC2 exhibited higher values (19.4 × 10 5 and 5.50 × 10 5 M − 1 ) of K b . Gel electrophoresis assay displayed that CT-DNA had a limited cleavage ability when metal complexes with different activators were present. Fluorescence technique also verified the interaction of the complexes with CT-DNA and BSA to demonstrate greater K b values (2.84 × 10 4 and 6.42 × 10 4 M − 1 ) of the derivatives TiC1 and TiC2 . DPPH assay was carried out to determine the radical scavenging activity of the complexes, so in-vitro cytotoxic effect on malignant cell lines was investigated by MTT Assay with MCF7 and HeLa cell lines, where complexes were observed as potent towards the HeLa cell line only. The potent TiC2 and TiC8 were screened with MTT assay against a normal HEK-293 cell line and were found to be inactive as expected. Subsequently, dual staining with acridine orange (AO) and ethidium bromide (EB) was performed to determine the cell death. Eventually, intracellular ROS was determined by DCFDA staining followed by cell cycle analysis was carried out using propidium iodide (PI) by flow cytometry to determine the phases.