Cytotoxic Pt(II) complexes containing alizarin: a selective carrier for DNA metalation.

Many efforts have been made in the last few decades to selectively transport antitumor agents to their potential target sites with the aim to improve efficacy and selectivity. Indeed, this aspect could greatly improve the beneficial effects of a specific anticancer agent especially in the case of orphan tumors like the triple negative breast cancer. A possible strategy relies on utilizing a protective leaving group like alizarin as the Pt(II) ligand to reduce the deactivation processes of the pharmacophore enacted by Pt resistant cancer cells. In this study a new series of neutral mixed-ligand Pt(II) complexes bearing alizarin and a variety of diamine ligands were synthesized and spectroscopically characterized by FT-IR, NMR and UV-Vis analyses. Three Pt(II) compounds, i.e., 2b, 6b and 7b, emerging as different both in terms of structural properties and cytotoxic effects (not effective, 10.49 ± 1.21 µM and 24.5 ± 1.5 µM, respectively), were chosen for a deeper investigation of the ability of alizarin to work as a selective carrier. The study comprises the in vitro cytotoxicity evaluation against triple negative breast cancer cell lines and ESI-MS interaction studies relative to the reaction of the selected Pt(II) complexes with model proteins and DNA fragments, mimicking potential biological targets. The results allow us to suggest the use of complex 6b as a prospective anticancer agent worthy of further investigations.

The Challenging Treatment of Cisplatin-Resistant Tumors: State of the Art and Future Perspectives.

One of the main problems in chemotherapy using platinum drugs as anticancer agents is the resistance phenomenon. Synthesizing and evaluating valid alternative compounds is challenging. This review focuses on the last two years of progress in the studies of platinum (II)- and platinum (IV)-based anticancer complexes. In particular, the research studies reported herein focus on the capability of some platinum-based anticancer agents to bypass resistance to chemotherapy, which is typical of well-known drugs such as cisplatin. Regarding platinum (II) complexes, this review deals with complexes in trans conformation; complexes containing bioactive ligands, as well as those that are differently charged, all experience a different reaction mechanism compared with cisplatin. Regarding platinum (IV) compounds, the focus was on complexes with biologically active ancillary ligands that exert a synergistic effect with platinum (II)-active complexes upon reduction, or those for which controllable activation can be realized thanks to intracellular stimuli.

Chiral 8-Amino-5,6,7,8-tetrahydroquinoline Derivatives in Metal Catalysts for the Asymmetric Transfer Hydrogenation of 1-Aryl Substituted-3,4-dihydroisoquinolines as Alkaloids Precursors.

Chiral diamines based on an 8-amino-5,6,7,8-tetrahydroquinoline backbone, known as CAMPY (L1), or the 2-methyl substituted analogue Me-CAMPY (L2) were employed as novel ligands in Cp* metal complexes for the ATH of a series of substituted dihydroisoquinolines (DHIQs), known for being key intermediates in the synthesis of biologically active alkaloids. Different metal-based complexes were evaluated in this kind of reaction, rhodium catalysts, C3 and C4, proving most effective both in terms of reactivity and enantioselectivity. Although modest enantiomeric excess values were obtained (up to 69% ee in the case of substrate I), a satisfactory quantitative conversion was successfully fulfilled even in the case of the most demanding hindered substrates when La(OTf)3 was used as beneficial additive, opening up the possibility for a rational design of novel chiral catalysts alternatives to the Noyori-Ikariya (arene)Ru(II)/TsDPEN catalyst.