👤 Singh VD

Synthesis of an entirely new series of arene ruthenium complexes [Ru(η6-C6H6)(L1)Cl]PF6, (1), [Ru(η6-C10H14)(L1)Cl]PF6 (2), [Ru(η6-C6H6)(L2)Cl]PF6 (3) and [Ru(η6-C10H14)(L2)Cl]PF6 (4) involving 5-[2-(1H-pyrazol-1-yl)quinoline]-BODIPY (L1) and 5-[6-methoxy-2-(1H-pyrazol-1-yl)quinoline]-BODIPY (L2) was described. The ligands and complexes were thoroughly characterized by various physicochemical techniques and the structures of L1, 1 and 4 were determined by X-ray single crystal analyses. Photo-/ and electrochemical property, DNA binding, cytotoxicity, cellular uptake and apoptotic studies on 1-4 were performed by various methods, while singlet oxygen-mediated cytotoxicity via photo-irradiation by visible light was supported by 1,3-diphenylisobenzofuran titration studies. Binding of the complexes in the minor groove of CT-DNA via van der Waals forces and electrostatic interactions was affirmed by molecular docking studies. In vitro antiproliferative activity and photocytotoxicity of 1-4 were examined against the human cervical cancer cell line (HeLa) which clearly showed that these are extremely photocytotoxic under visible light (400-700 nm, 10 J cm-2; IC50 49.15, 1; 25.18, 2; 15.85, 3; 12.87, 4), less toxic in the dark (IC50 > 100 μM) and preferentially accumulate in the lysosome of the HeLa cells. Further, these complexes behave as a potential theranostic agent and their ability to kill cancer cells under visible light lies in the order 4 > 3 > 2 > 1. Show less

The complex fac-[Re(CO)3(phendione)Cl] (1) (where phendione=1,10-phenanthroline-5,6-dione) has been synthesized and fully characterized by UV-visible, FTIR, and NMR techniques. The DNA binding properties of 1 are investigated by UV-spectrophotometric (melting curves), covalent binding assay, CV (cyclic voltammetry), circular dichroism (CD) and viscosity measurements. Experimental data indicate that 1 fits into the major groove without disrupting the helical structure of the B-DNA in contrast to the free phendione which intercalates within the base pairs of DNA. Upon irradiation, complex 1 promotes the cleavage of plasmid pBR322 DNA from supercoiled form I to nicked form II via a proton coupled electron transfer mechanism. This comes as a result of experimental data in anaerobic/aerobic conditions and in the presence of DMSO. The biological activities of 1 and its precursors [Re(CO)5Cl] and phendione are tested towards a series of cancerous cell lines as glioblastoma (T98G), prostate cancer (PC3) and breast cancer (MCF-7) as well as platelet activating factor (PAF)-aggregation. Moreover, all the aforementioned compounds are tested for their ability to modulate PAF-basic metabolic enzyme activities in preparations of rabbit leukolytes. The in vitro experiments indicate that phendione has a better antitumor effect than cisplatin whereas [Re(CO)5Cl] is a better PAF inhibitor than both the phendione ligand and 1. Moreover, for the first time it is indicated that [Re(CO)5Cl], with a IC50 of 17nM is comparable to the widely used PAF receptor antagonists, BN52021 and WEB2170 with IC50 of 30 and 20nM, respectively, whereas 1 affects PAF-catabolism. Show less