In this review, synthetic and mechanistic aspects of key methodologies that exploit C-C single-bond cleavage of strained ring systems are highlighted. The focus is on transition-metal-catalyzed processes that are triggered by C-C bond activation and β-carbon elimination, with the review concentrating on developments from mid-2009 to mid-2016.

[Cu(dap)2]Cl effectively catalyzes azide addition from the Zhdankin reagent to styrene-type double bonds, and subsequent addition of a third component to the benzylic position. In the presence of light, a photoredox cycle is implicated with polar components such as methanol or bromide adding to a benzylic cation. In the absence of light, by contrast, double azidation takes place to give diazides. Therefore, regioselective double functionalization can be achieved in good to excellent yields, with a switch between light and dark controlling the degree of azidation.

A three-component coupling of styrenes is reported, using photoredox catalysis to achieve simultaneous arylation and C-O or C-N bond formation across the styrene double bond.

An azidation method for C-N bond formation at benzylic C-H positions is described using copper-catalyzed visible light photochemistry and the Zhdankin azidoiodinane reagent. The method is applicable to a wide range of substrates bearing different functional groups and having a primary, secondary, or tertiary benzylic position, and is thought to proceed through a radical chain reaction.

A series of novel 1,4-diaryl-2-azetidinones were synthesized and evaluated for antiproliferative activity, cell cycle effects, and apoptosis induction. Strong cytotoxicity was observed with the best compounds (±)-trans-20, (±)-trans-21, and enantiomers (+)-trans-20 and (+)-trans-21, which exhibited IC(50) values of 3-13 nM against duodenal adenocarcinoma cells. They induced inhibition of tubulin polymerization and subsequent G2/M arrest. This effect was accompanied by activation of AMP-activated protein kinase (AMPK), activation of caspase-3, and induction of apoptosis. Additionally, the most potent compounds displayed antiproliferative activity against different colon cancer cell lines, opening the route to a new class of potential therapeutic agents against colon cancer.

Both activated normal and transformed lymphocytes produce not only cell-associated but also cell-free IL-2R. Evidence of high serum concentrations of IL-2R appears to serve as a tumor marker in patients with lymphomas On the contrary, the role of soluble IL-2R in solid neoplasms has still to be defined. This investigation was carried out to analyze soluble IL-2R production in human solid tumors. The study included 35 patients with solid tumors (12 without and 23 with metastases), 58 healthy subjects and 6 lymphoma patients. Among cancer patients, lung and breast carcinoma were the two most frequent neoplasms. In each subject or patient, serum levels of IL-2R were measured by using an enzyme immunoassay. Moreover, in 14/23 patients with metastatic solid tumors, lymphocyte subpopulations were also evaluated. Serum levels of IL-2R were significantly higher in the cancer patients than in the normal subjects. The patients with metastatic solid tumors showed significantly higher mean levels than those without metastases, and similar to those observed in the lymphoma patients. Finally, there was no correlation between serum levels of IL-2R and the T4/T8 ratio, which was reduced in 5/14 cancer patients. Further studies will be needed to establish if elevated concentrations of IL-2R in the serum can contribute to the immunoincompetence of patients with disseminated solid neoplasms.

No abstract

Sso7d is a small, basic, abundant protein from the thermoacidophilic archaeon Sulfolobus solfataricus. Previous research has shown that Sso7d can bind double-stranded DNA without sequence specificity by placing its triple-stranded L L-sheet across the minor groove. We previously found RNase activity both in preparations of Sso7d purified from its natural source and in recombinant, purified protein expressed in Escherichia coli. This paper provides conclusive evidence that supports the assignment of RNase activity to Sso7d, shown by the total absence of activity in the single-point mutants E35L and K12L, despite the preservation of their overall structure under the assay conditions. In keeping with our observation that the residues putatively involved in RNase activity and those playing a role in DNA binding are located on different surfaces of the molecule, the activity was not impaired in the presence of DNA. If a small synthetic RNA was used as a substrate, Sso7d attacked both predicted double-and single-stranded RNA stretches, with no evident preference for specific sequences or individual bases. Apparently, the more readily attacked bonds were those intrinsically more unstable. ß