engleski

Hybrid molecules as potential anticancer drugs: platinum complexes with diazenecarboxamides

Combined drugs that impact multiple targets simultaneously could better control complex disease such as cancer. In order to further improve the efficiency of using a two-drug cocktail, one approach involves the use of the so-called hybrid molecules, which comprises the incorporation of two drugs covalently bound into a single entity that combines pharmacological effects of independently acting drugs. Platinum coordination compounds are among the most utilized anticancer agents. We have shown previously that diazenecarboxamides are cytotoxic for different tumor cell lines, act synergistically with cisplatin, deplete glutathione (GSH), and may activate alternative cell-death pathways. The above results urge for the design and screening an array of different platinum complexes with diazenecarboxamide carrier groups. Because the synthesis of a diverse library of ligands capable of binding to platinum(II) is cumbersome, in this work we used an alternative approach for the functionalization of organic compounds with different ligand. It is based on recently discovered copper-catalyzed azide-alkyne cycloaddition protocol, also known as “Click chemistry”. Here we present the synthesis and biological evaluation of a number of cisplatin and carboplatin complexes with diazenecarboxamides. The cytotoxic activity was determined by spectrophotometric MTT assay using human cervical carcinoma HeLa cells as a model system. From examined new compounds, several were significant cytotoxic, however, none of them was more cytotoxic than carboplatin or cisplatin. In order to increase the activity of new compound, our further efforts will be focused at improving their solubility in aqueous media as this appears to be their major disadvantage.

Hybrid molecules ; cisplatin ; diazenecarboxamides ; anticancer compound ; tumor cells

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