Cellular uptake, cytotoxicity, apoptosis, DNA-binding, photocleavage and molecular docking studies of ruthenium(II) polypyridyl complexes.

Three new mononuclear [Ru (phen)2 ptip](2+) (1), [Ru (bpy)2 ptip](2+) (2) and [Ru (dmb)2 ptip](2+) (3) [ptip=(2-(5-phenylthiophen-2-yl)-1H-imidazo[4, 5-f][1,10 phenanthroline, phen=1, 10 phenanthroline, bpy=2, 2' bipyridine, dmb=4, 4'-dimethyl 2, 2' bipyridine] complexes were synthesized and characterised by elemental analysis, IR, NMR and Mass spectra. The DNA-binding behaviours were investigated by electronic absorption titration, luminescence spectra, viscosity measurements and photo-activated cleavage. The DNA-binding constants Kb of complexes 1, 2 and 3 were determined to be 7.0 (± 0.06)× 10(5), 3.87 (± 0.04) × 10(5), 2.79 (±0.07) × 10(5) respectively. The results showed that these complexes interact with CT-DNA by intercalative mode. Cell viability experiments indicated that the Ru(II) complex showed significant dose-dependent cytotoxicity to HeLa tumour cell lines. Further flow cytometry experiments showed that the cytotoxic Ru(II) complex induced apoptosis of HeLa tumour cell lines. Our data demonstrated that the Ru(II) polypyridyl complex binds to DNA and thereby induces apoptosis in tumor cells, suggesting that anti-tumor activity of the Ru(II) complex could be related to its interaction with DNA. The molecular dynamic simulations and docking methods were used to predict the DNA binding affinity of ruthenium complexes and with good visualisation images supporting with experimental results.

Cellular uptake, cytotoxicity, apoptosis and DNA-binding investigations of Ru(II) complexes.

Three new compounds, [Ru(Hdpa)2PyIP](ClO4)2·2H2O (1) [Ru(Hdpa)2FyIP](ClO4)2·2H2O (2) and [Ru(Hdpa)2IIP](ClO4)2·2H2O (3) have been synthesized and characterized by spectroscopic techniques such as elemental analysis, UV/Vis, FT-IR, (1)H NMR, (13)C NMR and mass spectra. The CT-DNA binding properties of 1-3 have been investigated by absorption, emission spectroscopy and viscosity measurements. Experimental results suggested that they can interact with DNA through intercalative mode with different binding strengths. These were found to promote the cleavage of plasmid DNA. Cell viability results indicated that all compounds showed significant dose dependent cytotoxicity in selected cell lines and 1 shown higher cytotoxicity than cisplatin on HeLa cells. Cellular uptake studies were studied by flow cytometry and confocal microscopy.

Synthesis and anticancer activity of chalcone-pyrrolobenzodiazepine conjugates linked via 1,2,3-triazole ring side-armed with alkane spacers.

Aiming to develop multitarget drugs for the anticancer treatment, a new class of chalcone-pyrrolo[2,1-c] [1,4]benzodiazepine (PBD) conjugates linked through a 1,2,3-triazole moiety containing alkane spacers has been designed and synthesized. Combining these two core pharmacophore structures with modifications at A-C8/C-C2-position of PBD ring system yielded analogs with improved efficacy and have shown promising in vitro anticancer activity ranging from <0.1-2.92 µM. These PBD-conjugates caused G1 cell cycle arrest with effect on G1 cell cycle regulatory proteins such as Cyclin D1 and Cdk4. These conjugates also exhibited inhibitory effect on NF-kB, Bcl-XL proteins that play a vital role in breast cancer cell proliferation. These findings suggest that one of the compound 4d among this series is most effective and has potential for detailed investigations.

Synthesis and biological evaluation of glycal-derived novel tetrahydrofuran 1,2,3-triazoles by 'click' chemistry.

Thirteen new 1,2,3-triazoles (5a-e, 15a-d, 17a-b, 19, and 21) were synthesized by 'click' reaction of sugar-derived azides with commercially available acetylenes. The synthesized triazoles were tested in vitro for their biological activity, and compound 5b displayed both antibacterial and antifungal activities at an MIC value of 12.5 microg/mL, while compounds 15b and 19 showed antibacterial activity at an MIC value of 25 microg/mL.