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

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 (1H and13C), UV-Vis, FT-IR and ESI-mass...

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Main Authors: Shivabasayya V. Salimath, Kavita B. Hiremath, Sathish Thanigachalam, Arjita Ghosh, Selva Kumar Ramasamy, Anbalagan Moorthy, S. K. Ashok Kumar, Murugesh Shivashankar, Madhvesh Pathak
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-13995-0
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author Shivabasayya V. Salimath
Kavita B. Hiremath
Sathish Thanigachalam
Arjita Ghosh
Selva Kumar Ramasamy
Anbalagan Moorthy
S. K. Ashok Kumar
Murugesh Shivashankar
Madhvesh Pathak
author_facet Shivabasayya V. Salimath
Kavita B. Hiremath
Sathish Thanigachalam
Arjita Ghosh
Selva Kumar Ramasamy
Anbalagan Moorthy
S. K. Ashok Kumar
Murugesh Shivashankar
Madhvesh Pathak
author_sort Shivabasayya V. Salimath
collection DOAJ
description 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 (1H and13C), 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 × 105 and 5.50 × 105 M− 1) of Kb. 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 Kb values (2.84 × 104 and 6.42 × 104 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.
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spelling doaj-art-2e73ec553f2341aeafad60324b566c152025-08-20T03:04:25ZengNature PortfolioScientific Reports2045-23222025-08-0115112910.1038/s41598-025-13995-0In-vitro antiproliferative evaluation of newly synthesized titanium(IV) metallacyclic complexes on HeLa and MCF7 cell linesShivabasayya V. Salimath0Kavita B. Hiremath1Sathish Thanigachalam2Arjita Ghosh3Selva Kumar Ramasamy4Anbalagan Moorthy5S. K. Ashok Kumar6Murugesh Shivashankar7Madhvesh Pathak8Department of Chemistry, School of Advanced Sciences (SAS), Vellore Institute of Technology (VIT)Department of Chemistry, School of Advanced Sciences (SAS), Vellore Institute of Technology (VIT)Department of Chemistry, School of Advanced Sciences (SAS), Vellore Institute of Technology (VIT)Department of Integrative Biology, School of Bioscience and Technology (SBST), Vellore Institute of Technology (VIT)Department of Chemistry, M.M. Engineering College, Maharishi Markandeshwar (Deemed to be University)Department of Integrative Biology, School of Bioscience and Technology (SBST), Vellore Institute of Technology (VIT)Department of Chemistry, School of Advanced Sciences (SAS), Vellore Institute of Technology (VIT)Department of Chemistry, School of Advanced Sciences (SAS), Vellore Institute of Technology (VIT)Department of Chemistry, School of Advanced Sciences (SAS), Vellore Institute of Technology (VIT)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 (1H and13C), 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 × 105 and 5.50 × 105 M− 1) of Kb. 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 Kb values (2.84 × 104 and 6.42 × 104 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.https://doi.org/10.1038/s41598-025-13995-0
spellingShingle Shivabasayya V. Salimath
Kavita B. Hiremath
Sathish Thanigachalam
Arjita Ghosh
Selva Kumar Ramasamy
Anbalagan Moorthy
S. K. Ashok Kumar
Murugesh Shivashankar
Madhvesh Pathak
In-vitro antiproliferative evaluation of newly synthesized titanium(IV) metallacyclic complexes on HeLa and MCF7 cell lines
Scientific Reports
title In-vitro antiproliferative evaluation of newly synthesized titanium(IV) metallacyclic complexes on HeLa and MCF7 cell lines
title_full In-vitro antiproliferative evaluation of newly synthesized titanium(IV) metallacyclic complexes on HeLa and MCF7 cell lines
title_fullStr In-vitro antiproliferative evaluation of newly synthesized titanium(IV) metallacyclic complexes on HeLa and MCF7 cell lines
title_full_unstemmed In-vitro antiproliferative evaluation of newly synthesized titanium(IV) metallacyclic complexes on HeLa and MCF7 cell lines
title_short In-vitro antiproliferative evaluation of newly synthesized titanium(IV) metallacyclic complexes on HeLa and MCF7 cell lines
title_sort in vitro antiproliferative evaluation of newly synthesized titanium iv metallacyclic complexes on hela and mcf7 cell lines
url https://doi.org/10.1038/s41598-025-13995-0
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