Influence of substituents on DNA and protein binding of cyclometalated Ir(iii) complexes and anticancer activity. Issue 26 (22nd June 2017)

• Record Type: Journal Article
• Authors: Mukhopadhyay, Sujay; Singh, Roop Shikha; Paitandi, Rajendra Prasad; Sharma, Gunjan; Koch, Biplob; Pandey, Daya Shankar
• Is Part Of: Dalton transactions. Volume 46:Issue 26(2017)
• Page Start: 8572
• Page End: 8585
• Publication Date: 2017-06-22
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/c7dt01015j
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : Three cyclometalated Ir(iii ) complexes based on terpyridyl ligands have been efficiently used for DNA and protein binding studies as well as anticancer activity against HeLa cell lines. Abstract : Synthesis of terpyridyl based ligands 3-([2, 2′:6′, 2′′-terpyridin]-4′-yl)-7-methoxy-2-(methylthio)-quinolone, (L1 ); 3-([2, 2′:6′, 2′′-terpyridin]-4′-yl)-6-methoxyquinolin-2(1 H )-one, (L2 ); 3-([2, 2′-:6′, 2′′-terpyridin]-4′-yl)-6-methylquinolin-2(1 H )-one (L3 ) and cyclometalated iridium(iii ) complexes [[Ir(ppy)2 L1 ] + PF6 − (1 ), [Ir(ppy)2 L2 ] + PF6 − (2 ), [Ir(ppy)2 L3 ] + PF6 − (3 ) (2-phenylpyridine = Hppy)] involving these ligands has been described. The ligandsL1–L3 and complexes1–3 have been thoroughly characterized by elemental analyses, spectral studies (IR, 1 H, 13 C NMR, UV/vis and fluorescence) ESI-MS, and the structure of3 has been unambiguously authenticated by single crystal X-ray analyses. UV/vis, fluorescence and circular dichroism spectroscopic studies showed rather efficient binding of1 with CT-DNA (calf thymus DNA) and BSA (bovine serum albumin) relative to2 and3 . Molecular docking studies unveiled binding of1–3 with minor groove of CT-DNA via van der Waal's forces and electrostatically with the hydrophobic moiety of HSA (human serum albumin). The ligands and complexes exhibited moderate cytotoxicity towards MDA-MB-231 (breast cancer cell line) and significant influence on HeLa (cervical cancer cell line) cells. Cytotoxicity, morphological changes, and apoptosis have been followed by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide) assay, Hoechst 33342/PI (PI = propidium iodide) staining, cell cycle analysis by FACS (fluorescence activated cell sorting), and ROS (reactive oxygen species) generation by DCFH-DA (dichlorodihydrofluorescein diacetate) dye. Confocal microscopy images revealed that the drug efficiently initiates apoptosis in the cell cytosol. The IC50 values showed superior cytotoxicity of1–3 against the HeLa cell line relative to cisplatin, and their ability to induce apoptosis is in the order1 >2 >3 .