Bioactive Salen-type Schiff Base Transition Metal Complexes as Possible Anticancer Agents.

Although metal-based anticancer drugs have been recognized as the most effective agents over the organic compounds, non-selectivity and high toxic effects have limited their applications in a way that only three Pt-analogues have progressed into clinical use. These problems have spurred chemists to develop different strategies based on alternative targets. This work focuses on predicting potency and mode of interactions of a series of salen type Schiff base transition metal complexes derived from meso-1,2-diphenyl-1,2-ethylenediamine, over some proteins (HDAC7, HDAC2, CatB, B-RAF kinase, TopII, RNR, TS, and rHA) using computational docking method, to be later considered as possible anticancer agents. The obtained results showed that all complexes exhibited higher affinity for HDAC7 than the other targets. Moreover, the bromo-derivatives of the copper compounds were more active on HDAC7 than the other derivatives. Such bromo compounds showed considerable interactions with Kinase, RNR, TS, and CatB. Contrary to Histone deacetylase (HAD)C7; HDAC2 was predicted to be relatively poor target. As expected, formation of the hydrophobic interactions between the metal complexes and the protein targets were essential for activity of the metal compounds. This study provides some more information for further optimizations and development of new metallodrugs as enzyme inhibitors for potential therapeutic agents.

Breast cancer cells imaging by targeting methionine transporters with gadolinium-based nanoprobe.

PURPOSE: Early cancer diagnosis using MRI imaging is of high global interest as a non-invasive and powerful modality. In this study, methionine was conjugated on gadolinium-based mesoporous silica nanospheres to evaluate intra-cellular uptake and its accumulation in human breast cancer cells. PROCEDURES: The contrast agent was synthesized and characterized using different techniques including N2 physisorption, thermal gravimetric analysis, dynamic light scattering, and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The intra-cellular uptake of Gd(3+) was measured by ICP-AES, fluorescent microscopy, and flow cytometry. Finally, cellular and tumor MR imaging were performed to determine in vitro and in vivo relaxometry. RESULTS: According to the results, the contrast agents accumulated in tumor cells both in vitro and in vivo. There was no significant cellular toxicity on either normal or cancer cells along with strong intense signal on T 1 compared to the unlabeled cells. CONCLUSIONS: The results showed that the novel contrast agent could become a useful tool in early detection of cancer.