Synthesis and biological activities of 4-N-(anilinyl-n-[oxazolyl])-7-chloroquinolines (n=3' or 4') against Plasmodium falciparum in in vitro models.

The synthesis (Pd-mediated coupling strategy) and characterization (NMR, IR, elemental analysis, etc.) of a short series of quinoline-oxazole hybrid compounds has been carried out. These materials are found to be moderately active against Plasmodium falciparum in vitro, with activities in the sub-micromolar range, and to display acceptable cytotoxicity to mononuclear leukocytes. Chemical modification strategies, with the intention to increase the biological potency of this new class of anti-malarial agents, are discussed.

Platinum(II) and palladium(II) complexes with 2-acetyl pyridine 4N-ethyl thiosemicarbazone able to overcome the cis-platin resistance. Structure, antibacterial activity and DNA strand breakage.

The reactions of Pd(II) and Pt(II) with 2-Acetyl Pyridine N(4)-Ethyl-Thiosemicarbazones, HAc4Et and 2-Acetyl Pyridine N(4)-1-(2-pyridyl)-piperazinyl Thiosemicarbazone, HAc4PiPiz and 2-Formyl Pyridine N(4)-1-(2-pyridyl)-piperazinyl Thiosemicarbazone, HFo4PiPiz afforded the complexes, [Pd(Ac4Et)], 1, [Pd(HAc4Et)2]Cl2, 2 and [Pd(Ac4Et)2], 3 [Pt(Ac4Et)], 4, [Pt(HAc4Et)2]Cl2, 5, [Pt(Ac4Et)2], 6 and [Pd(Fo4PipePiz)Cl], 7, [Pd(Fo4PipePiz)2], 8, [Pd(Ac4PipePiz)Cl], 9 and [Pd(Ac4PipePiz)2], 10. The crystal structure of the complex [Pt(Ac4Et)2], 6 has been solved. The platinum(II) atom is in a square planar environment surrounded by two cis nitrogen atoms and two cis sulfur atoms. The ligands are not equivalent, one being tridentate with (N,N,S) donation, the other being monodentate using only the sulfur atom to coordinate to the metal. The tridentate ligand shows a Z, E, Z configuration while the monodentate ligand shows an E, E, Z. Inter-molecular hydrogen bonds stabilize the structure, while the crystal packing is determined by pi-pi, and Pt-C interactions. The antibacterial effect of Pd(II) and Pt(II) complexes were studied in vitro. The complexes were found to have effect on Gram(+) bacteria, while the same complexes showed no bactericidal effect on Gram(-) bacteria. The effect of the Pd(II) and Pt(II) complexes on the in vitro DNA strand breakage was studied by agarose gel electrophoresis. The complexes 1-6 were found to exhibit a cytotoxic potency in a very low micromolar range and to be able to overcome the cisplatin resistance of A2780/Cp8 cells.