Antiproliferative effect and genotoxicity of novel synthesized palladium complexes with organoarsenic ligands.
Three new palladium complexes with general formula [PdCl(2)L(2)], where L=heterofunctional organoarsenic ligand: (2-isopropoxyphenyl)diphenylarsine (1), (2-methoxyphenyl)-diphenylarsine (2) and (2-hydroxyphenyl)diphenylarsine (3) have been synthesized and fully characterized, including X-ray crystallographic data. Their potential antitumor effect and genotoxicity have been studied as well. The viability test performed on human tumor (MLS) and normal (Hfl-1) cell lines indicates significant cytotoxicity of complexes, which is higher in tumor cells than in normal cells. The lethal doses are comparable with those of standard metal-based chemotherapeutical drugs (carboplatin and oxaliplatin). These palladium complexes exhibit a higher cytotoxicity against tumor cells as against normal cells in vitro. A new static cytometric method was developed and simultaneously the classic AnnexinV test was performed. Complex 2 has an important capacity to induce apoptosis in tumor cells. The apoptotic process is triggered due to the interaction of these complexes with secondary structure of DNA in treated cells. The alkaline single-cell gel assay shows that the level of DNA damages induced by compounds 2 and 3 are significantly higher in tumor cells as in normal cells. These studies shown that complexes 1, 2 and 3 have biologic activity, the effect of complex 2 being superior to its platinum analogues, attributable to its structure.
Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Kalinciakova 8, Bratislava 83232, Slovakia. miklasova@fpharm.uniba.sk
Natalia
N
Miklásová
Eva
E
Fischer-Fodor
Peter
P
Lönnecke
Maria Perde
MP
Schrepler
Piroska
P
Virag
Corina
C
Tatomir
Valentin Ioan
VI
Cernea
Evamarie
E
Hey-Hawkins
Luminiţa
L
Silaghi-Dumitrescu
D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D001152:Arsenicals / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004249:DNA Damage; D006801:Humans; D008024:Ligands; D010165:Palladium / Q000737:chemistry / Q000494:pharmacology*
D017304:Annexin A5; D000970:Antineoplastic Agents; D001152:Arsenicals; D008024:Ligands; D010165:Palladium