ABSTRACT
Azocarboxamide (azcH) has been combined for the first time with [Ru-Cym] to generate metal complexes with N,N- and N,O-coordination mode, [(Cym)Ru(azc)Cl] and [(Cym)Ru(azcH)Cl](+) [PF6 ](-). Geometric and electronic structures of the complexes are reported along with their in vitro activities against different tumour cell lines and preliminary results on solution chemistry. Compound [(Cym)Ru(azc)Cl] exhibited remarkable cytotoxic properties. It was cell-type specific and had comparable IC50 values towards both cancer cells and their drug-resistant subline. A tenfold increase in the sensitivity towards [(Cym)Ru(azc)Cl] was noted for the tumour cells with depleted intracellular glutathione (GSH) level, suggesting the essential role of GSH in cell response to this compound.
Subject(s)
Antineoplastic Agents/chemistry , Aza Compounds/chemistry , Coordination Complexes/chemistry , Glutathione/chemistry , Ruthenium/chemistry , Antineoplastic Agents/toxicity , Cell Line, Tumor , Coordination Complexes/toxicity , Crystallography, X-Ray , Humans , Models, MolecularABSTRACT
To increase the effectiveness of cancer treatment, more effective anti-cancer drugs, as well as the new improved strategies of cancer treatment, are urgently needed. Our previous results have shown that various diazenes are cytotoxic to different tumor cells and can even revert the resistance to cisplatin and vincristine. We also demonstrated that unsymmetrical diazenedicarboxamides 1 and 2 exhibited promising cytotoxicity. The aim of the present study was to synthesize new diazenedicarboxamides with acceptable solubility and good cytotoxicity. Here we report the synthesis and biological evaluation of new N,N'-disubstituted diazenedicarboxamides. We found that a modification of either 1 or 2 led to the more active compounds. The most effective among them was diazenedicarboxamide 11, which can be considered as a new potential anticancer agent for the tumors of different origin, as well as for the drug resistant tumors.
