Pyrimidinone Associated Triazole Carboxamides: Synthesis, Characterization, Cytotoxicity and DNA Binding Studies

Background: Pyrimidinones and its derivatives are present in many anti-cancer agents. It has been reported that these substances were proven to have significant activities against different types of human cancers. The incorporation of [1,2,3]-triazole, a nitrogen-rich unit not only increases the efficacy but also increases the lipophilicity of the drug molecule. As our research was to synthesize newer molecules of effective cytotoxicity, we focused on pyrimidinone and [1,2,3]-triazoles systems, as important scaffolds with the expectation of potential cytotoxic properties. Methods: Novel series of [1,2,3]-triazole carboxamides (5a-j) were synthesized, starting from 3-(2- chloroethyl)-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one. The structure of all the synthesized compounds was elucidated based on IR, 1H-NMR, 13C-NMR and LC-MS data. Compounds were focused for their in vitro cytotoxicity against A375 melanoma cancer cell lines, MDA-MB-231 breast cancer cell lines and HEK 293-Human embryonic kidney cell lines using colorimetric MTT assay. The potent compound was evaluated for the DNA binding studies. Results: Most of the Pyrimidinone conjugated [1,2,3]-triazole carboxamides found to be selective towards melanoma cancer cell lines than breast cancer cell lines. Compounds 5d, 5i and 5b were effective against A375 cancer cell lines and are found to be non-toxic against HEK 293-Human embryonic kidney cell lines. The potent compound 5d showed good intrinsic binding constant (Kb) value 3.12 x 103 M-1 in UV based DNA titration. Conclusion: Newly synthesized Pyrimidinone conjugated [1,2,3]-triazole carboxamide derivatives showed the significant cytotoxicity and the potent compound showed good intrinsic binding constant in UV based DNA titration.

Synthesis, structure, DNA binding and anticancer activity of a new tetranuclear Pb(II) complex constructed by 8-hydroxyquinolinate and 4-nitrobenzoate ligands

A new Pb(II) complex, [Pb(8-OQ)(4-NB)], where 8-OQ = 8-hydroxyquinolinate, 4-NB = 4-nitrobenzoate, has been synthesized and characterized by elemental analysis, IR spectroscopy, and X-ray single-crystal diffraction. The single crystal X-ray analysis reveals that the complex possesses a tetranuclear Pb4O4 cubane structure. The Pb(II) atom is coordinated by three triply bridging phenolic hydroxyl O atoms of 8-OQ ligands, then the tetranuclear Pb system is formed resulting in a tetrahedral cage. The interaction of complex with HS-DNA in Tris buffer was studied by UV−vis absorption spectrum and fluorescence ethidium bromide displacement experiment with an intrinsic binding constant of 1.52×104 M-1 and a linear Stern–Volmer quenching constant of 6.77×103 M-1. Anticancer activity against MCF-7, HepG-2 and A549 cell lines of complex was also determined by the MTT-based assay. The results showed the complex can inhibit proliferation of these three kinds of tumor cells and is less cytotoxic than cisplatin.

Synthesis, spectral, dna binding and cleavage properties of ruthenium(II) Schiff base complexes containing PPh3/AsPh3 as co-ligands

A dihydroxybenzaldehyde Schiff base ligands (L1-L3) and its ruthenium(II) complexes, have been synthesized and characterized on the basis of elemental analysis, 1H, 13C, 31P NMR, mass spectra, UV-vis and IR spectra. The binding of ruthenium(II) complexes have been investigated by UV-vis absorption spectroscopy. The experiment reveals that all the compounds can bind to DNA through an electrostatic mode and intrinsic binding constant (Kb) has been estimated under similar set of experimental conditions. Absorption spectral study indicate that the ruthenium(II) complexes has intrinsic binding constant in the range of 1.6-8.6 X 104 M-1. The complex [Ru(CO)(PPh3)2(L3)] bind more strongly than that of the other complexes. In addition, DNA cleavage property were tested for all ruthenium(II) complexes.

Tryptanthrin Sulfonate: Crystal Structure, Cytotoxicity and DNA Binding Studies

Tryptanthrin (TPT), which is an indoloquinazoline alkaloid with multiple biological activities, was studied on its sulfonation in order to increase its water solubility. An 8-substituted tryptanthrin sulfonate (TPTS) was synthesized and structurally characterized by IR, 1H-NMR, ESI-MS, as well as X-ray single crystal diffraction analysis. The interactional mechanism of TPTS with calf thymus DNA (ctDNA) was further studied by UV spectroscopy and DNA viscosity experiment. The addition of ctDNA into the TPTS solution induced moderate hypochromicity on its electronic absorption spectrum, by which an intrinsic binding constant of 1.10×104 M-1 was achieved. While addition of TPTS caused significant increasement on the viscosity of ctDNA solution. The results suggest that TPTS interacts with ctDNA mainly by intercalative binding mode.