ABSTRACT
The reactions of 2-acetylpyridine N(4)-methyl, (HAc4Me) N(4)-ethyl (HAc4Et) and N(4)-Phenyl (HAc4Ph) thiosemicarbazone with palladium(II) were studied. The ligands and the palladium(II) complexes have been characterized by spectroscopic techniques. The structure of [Pd(Ac4Me)Cl] has been determined by single-crystal x-ray diffraction. The protonation constants of HAc4Me and HAc4Et, Ka1 and Ka2, were determined by spectrophotometry. The effect of palladium compounds on DNA synthesis of P388 and L1210 cell cultures is also reported. Some of these compounds increased the life span of mice bearing tumors.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacology , Palladium/pharmacology , Thiosemicarbazones/chemistry , Thiosemicarbazones/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Crystallization , Drug Screening Assays, Antitumor , Leukemia, Experimental/drug therapy , Magnetic Resonance Spectroscopy , Male , Mice , Mice, Inbred Strains , Models, Molecular , Organometallic Compounds/chemical synthesis , Spectrophotometry , Structure-Activity Relationship , Thiosemicarbazones/chemical synthesisABSTRACT
The effect of novel Pd(II) complexes with derivatives of 2-acetyl-pyridinethisemicarbazone, N4-ethyl (HAc4Et) and 3-hexamethyleneiminylthiosemicarbazone (HAchexim), on Sister Chromatid Exchange (SCE) rates and human lymphocyte proliferation kinetics was studied. Also, the effect of Pd(II) complexes on DNA synthesis of P388 and L1210 cell cultures and against Leukemia P388 was investigated. Among these compounds, the compound Bis(3-hexamethyleneiminyl-2-acetylpyridine-thisemicarbazonato++ +) palladium (II) was found to be distinctly effective against Leukemia P388, in inhibiting incorporation of 3H-thymidine into DNA and in inducing SCEs and cell division delays.
