Investigation of the pharmacological profiles of dinuclear metal complexes as novel, potent and selective cytotoxic agents against ras-transformed cells.
Around the world scientists try to design successful cures against still incurable diseases, especially cancers. New targets for prevention and new agents for therapy need to be identified. We synthesized novel metal complexes [Au(L1)(L2)Pt]Cl2 and [Ru(L1)2(L2)Pt]Cl2 for determining their cytotoxic and apoptotic effects. The complexes are synthesized by using 1,8-diaminonaphthalene (L1), and bis-1,4-di[([1,10]phenanthroline-5-il)aminomethyl]cyclohexane (L2) as ligands. This is the first study to examine these metals and these molecules in cancer treatment. We elucidated the effects of test compounds with embryonic rat fibroblast-like cells (F2408) and H-ras oncogene activated embryonic rat fibroblast-like cancer cells (5RP7). Results showed that our complexes are more effective than cisplatin to kill ras-transformed cells. Although the [Au(L1)(L2)Pt]Cl2 compound showed a cytotoxic potency higher than [Ru(L1)2(L2)Pt]Cl2 against cancer cells, it proved to be almost five times less effective in decreasing cell viability over healthy cells. Au(III) compound selectively targets the cancer cells but not the healthy cells.
Anadolu University, Faculty of Sciences, Department of Biology, 26470 Eskişehir, Turkey. Electronic address: beklemb@gmail.com.
R Beklem
RB
Bostancıoğlu
Anadolu University, Faculty of Sciences, Department of Biology, 26470 Eskişehir, Turkey. Electronic address: akoparal@anadolu.edu.tr.
A Tansu
AT
Koparal
Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470 Eskisehir, Turkey. Electronic address: kbenkli@anadolu.edu.tr.
Kadriye
K
Benkli
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology*; D011905:Genes, ras; D006046:Gold / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D003603:Cytotoxins; D006046:Gold; D012428:Ruthenium
Antitumoral activity; Apoptosis; Au(III); Pt(II); Ru(II); Selective toxicity