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Carbon monoxide, the "silent killer" gas, is increasingly recognised as an important signalling molecule in human physiology, which has beneficial biological properties. A particular way of achieving controlled CO administration is based on the use of biocompatible molecules that only release CO when triggered by internal or external factors. These approaches include the development of pharmacologically effective prodrugs known as CO releasing molecules (CORMs), which can supply biological systems with CO in well-regulated doses. An overview of transition metal-based CORMs with cytotoxic properties is here reported. The mechanisms at the basis of the biological activities of these molecules and their potential therapeutical applications with respect to their stability and CO releasing properties have been discussed. The activation of metal-based CORMs is determined by the type of metal and by the nature and features of the auxiliary ligands, which affect the metal core electronic density and therefore the prodrug resistance towards oxidation and CO release ability. A major role in regulating the cytotoxic properties of these CORMs is played by CO and/or CO-depleted species. However, several mysteries concerning the cytotoxicity of CORMs remain as intriguing questions for scientists. [ABSTRACT FROM AUTHOR]

The cytotoxicity of two tricarbonyl Mn(I) complexes of the general formula fac-[MnBr(CO)3L] (L = quinoline-2-carboxaldehyde (A) and 8-amino quinoline (B)) towards triple negative breast cancer (MDA-MB-231) was reported. Complexes A and B released CO when exposed to 468 nm light. Compound B has a dose-dependent cytotoxicity, with half maximal inhibitory concentration values of 19.62 μM and 11.43 μM before and after illumination, respectively. Co-treatment of MDA-MB-231 with paclitaxel (30 nM) and complex B (10 μM) resulted in a 50% reduction in cell viability. [ABSTRACT FROM AUTHOR]

Reaction between [RuCl2(CO)2]n and 1H-benzimidazol-2-ylmethyl-(N-phenyl)amine ligands (LR) functionalized with various electron-donating and electron-withdrawing substituents on the phenyl ring (R = H, 4-CH3, 4-Cl, 4-COOCH3, and 3-COOCH3) afforded the dark-stable photoactivatable carbon monoxide prodrugs of the general formula [RuCl2(CO)2LR]. Release of the CO molecules from the Ru(II) compounds was examined by monitoring the electronic and IR spectra upon illumination at 365 nm. A noticeable decrease in the intensities of the two characteristic ν(C≡O) modes for Ru(CO) II2 species, and the growth of two new bands for the mono-carbonyl species and free CO, were the main features of the photolysis profiles. The cytotoxicity of the complexes towards breast cancer (MCF-7) cells was assessed with and without illumination at 365 nm. All the complexes except that with a 4-COOCH3 group (IC50 = 45.08 ± 3.5 μM) are nontoxic under dark conditions. Upon illumination, all the compounds acquired cytotoxicity in the following order: H > 4-COOCH3 > 4-CH3 > 4-Cl > 3-COOCH3. Investigation of the cytotoxicity of the CO-depleted fragments showed that the light-induced cytotoxicity can be attributed to the liberated CO and CO-depleted metal fragments, including the liberated benzimidazole ligands. [ABSTRACT FROM AUTHOR]