Chemical approaches for the enhancement of porphyrin skeleton-based photodynamic therapy.

With the development of photodynamic therapy (PDT), remarkable studies have been conducted to generate photosensitisers (PSs), especially porphyrin PSs. A variety of chemical modifications of the porphyrin skeleton have been introduced to improve cellular delivery, stability, and selectivity for cancerous tissues. This review aims to highlight the developments in porphyrin-based structural modifications, with a specific emphasis on the role of PDT in anticancer treatment and the design of PSs to achieve a synergistic effect on multiple targets.

Copper nitrate-catalyzed oxidative coupling of unactivated C(sp3)-H bonds of ethers and alkanes with N-hydroxyphthalimide: synthesis of N-hydroxyimide esters.

A copper nitrate-catalyzed cross-dehydrogenative coupling reaction between N-hydroxyphthalimide (NHPI) and ethers/alkanes has been described. The reaction is accomplished smoothly by using simple and green molecular oxygen as the oxidant, providing an alternative for the efficient synthesis of N-alkoxyphthalimides. In addition, it was found that when tert-butyl ethers were used as substrates, unexpected N-hydroxyimide ester derivatives were obtained in moderate to excellent yields. To further understand this unusual transformation, control experiments were performed and a plausible mechanism was proposed.

The Fe-S cluster assembly protein IscU2 increases α-ketoglutarate catabolism and DNA 5mC to promote tumor growth.

IscU2 is a scaffold protein that is critical for the assembly of iron-sulfur (Fe-S) clusters and the functions of Fe-S-containing mitochondrial proteins. However, the role of IscU2 in tumor development remains unclear. Here, we demonstrated that IscU2 expression is much higher in human pancreatic ductal adenocarcinoma (PDAC) tissues than in adjacent normal pancreatic tissues. In PDAC cells, activated KRAS enhances the c-Myc-mediated IscU2 transcription. The upregulated IscU2 stabilizes Fe-S cluster and regulates the activity of tricarboxylic acid (TCA) cycle enzymes α-ketoglutarate (α-KG) dehydrogenase and aconitase 2, which promote α-KG catabolism through oxidative and reductive TCA cycling, respectively. In addition to promoting mitochondrial functions, activated KRAS-induced and IscU2-dependent acceleration of α-KG catabolism results in reduced α-KG levels in the cytosol and nucleus, leading to an increase in DNA 5mC due to Tet methylcytosine dioxygenase 3 (TET3) inhibition and subsequent expression of genes including DNA polymerase alpha 1 catalytic subunit for PDAC cell proliferation and tumor growth in mice. These findings underscore a critical role of IscU2 in KRAS-promoted α-KG catabolism, 5mC-dependent gene expression, and PDAC growth and highlight the instrumental and integrated regulation of mitochondrial functions and gene expression by IscU2 in PDAC cells.