First-In-Class Thiosemicarbazone Metal Complexes Targeting the Sigma-2 Receptor (S2R) as an Innovative Strategy against Pancreatic Cancer.

Pancreatic cancer, with its increasing incidence and lowest 5-year survival rate, is predicted to become the second leading cause of cancer deaths by 2030. Current clinical trials have shown limited improvement, highlighting the need for new therapies. The sigma-2 receptor (S2R), with roles in tumor progression, is a target for novel thiosemicarbazones (TSCs).

Interactions with DNA Models of the Oxaliplatin Analog (-1,3-DACH)PtCl.

It is generally accepted that adjacent guanine residues in DNA are the primary target for platinum antitumor drugs and that differences in the conformations of the Pt-DNA adducts can play a role in their antitumor activity. In this study, we investigated the effect of the carrier ligand -1,3-diaminocyclohexane (-1,3-DACH) upon formation, stability, and stereochemistry of the (-1,3-DACH)PtG and (-1,3-DACH)Pt(d(GpG)) adducts (G = 9-EthlyGuanine, guanosine, 5'- and 3'-guanosine monophosphate; d(GpG) = deoxyguanosil(3'-5')deoxyguanosine). A peculiar feature of the -1,3-DACH carrier ligand is the steric bulk of the diamine, which is asymmetric with respect to the Pt-coordination plane.

Surface-Engineered Cesium Lead Bromide Perovskite Nanocrystals for Enabling Photoreduction Activity.

In recent years, colloidal lead halide perovskite (LHP) nanocrystals (NCs) have exhibited such intriguing light absorption properties to be contemplated as promising candidates for photocatalytic conversions. However, for effective photocatalysis, the light harvesting system needs to be stable under the reaction conditions propaedeutic to a specific transformation. Unlike photoinduced oxidative reaction pathways, photoreductions with LHP NCs are challenging due to their scarce compatibility with common hole scavengers like amines and alcohols.

Cytotoxic pathways activated by multifunctional thiosemicarbazones targeting sigma-2 receptors in breast and lung carcinoma cells.

Background: Multifunctional thiosemicarbazones (TSCs) able to bind sigma receptors and chelate metals are considered as a promising avenue for the treatment of pancreatic cancer due to the encouraging results obtained on in vitro and in vivo models. Here, we assessed the biochemical mechanism of these TSCs also on lung (A549) and breast (MCF7) cancer cells.

Methods: The density of sigma-2 receptors in normal (BEAS-2B and MCF10A) and in lung and breast (A549 and MCF7) cancer cells was evaluated by flow cytometry.

The mechanism of antiproliferative activity of the oxaliplatin pyrophosphate derivative involves its binding to nuclear DNA in cancer cells.

(1R,2R-diaminocyclohexane)(dihydropyrophosphato) platinum(II), also abbreviated as RRD2, belongs to a class of potent antitumor platinum cytostatics called phosphaplatins. Curiously, several published studies have suggested significant mechanistic differences between phosphaplatins and conventional platinum antitumor drugs. Controversial findings have been published regarding the role of RRD2 binding to DNA in the mechanism of its antiproliferative activity in cancer cells.