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[reaction: see text] Olefinic sulfamates derived from primary and secondary alcohols undergo intramolecular copper-catalyzed aziridination in the presence of iodosylbenzene to afford novel bicyclic fused aziridines. The latter were opened by various nucleophiles to give the corresponding substituted cyclic sulfamates, which in turn reacted, after nitrogen activation, with a second nucleophile at the carbon atom bearing the oxygen atom. Concomitant removal of the sulfonyloxy moiety thus gave access to polysubstituted amines.

The reaction between [(C 6 F 5 ) 2 Pt(µ-PPh 2 ) 2 Pt(PPh 2 R) 2 ] and [Pt(C 7 H 10 ) 3 ] in toluene yields the triangulo complexes [Pt 3 (µ-PPh 2 ) 2 (µ-C 6 F 5 )(C 6 F 5 )(PPh 2 R) 2 ] (R ) Ph 4, Me 5, Et 6), which contain two phosphido and one pentafluophenyl bridging ligands and two phosphines and one pentafluophenyl terminal ones. The triangulo metal core displays three Pt-Pt bonds, as expected for a 42 valence electron count cluster. The basicity of these metal cores is demonstrated through the reaction of one of the complexes (R ) Ph) with AgClO 4 or [Ag-(OClO 3 )(PPh 3 )], which gives the corresponding adduct [Pt 3 (AgOClO 3 )(µ-PPh 2 ) 2 (µ-C 6 F 5 )(C 6 F 5 )-(PPh 3 ) 2 ] (7) or [Pt 3 Ag(µ-PPh 2 ) 2 (µ-C 6 F 5 )(C 6 F 5 )(PPh 3 ) 3 ][ClO 4 ] (8). The X-ray structures of 4 and 7 have been determined.

Two cucurbitacins, dihydrocucurbitacin B (1) and cucurbitacin B (2), which can be obtained in large amounts from the roots of Wilbrandia ebracteata and from the fruits of Luffa operculata, respectively, were used as starting materials for the preparation of a library of 29 semi-synthetic derivatives. The structural changes that were performed include the removal, modification or permutation of functional groups in rings A and B as well as in the side chain. All new semisynthetic compounds, as well as 1 and 2, were tested in vitro for their cytotoxic effects on non-small-cell lung cancer cells (A549 cells). Some of these compound displayed potent to moderate activity against A549 tumor cells, especially those cucurbitacin B derivatives which were modified at ring A.

Lung cancer is the most deadly type of cancer in humans, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer showing high resistance to radiation and chemotherapy. Despite the outstanding progress made in anti-tumor therapy, discovering effective anti-tumor drugs is still a challenging task. Here we describe a new semisynthetic derivative of cucurbitacin B (DACE) as a potent inhibitor of NSCLC cell proliferation. DACE arrested the cell cycle of lung epithelial cells at the G2/M phase and induced cell apoptosis by interfering with EGFR activation and its downstream signaling, including AKT, ERK, and STAT3. Consistent with our in vitro studies, intraperitoneal application of DACE significantly suppressed the growth of mouse NSCLC that arises from type II alveolar pneumocytes due to constitutive expression of a human oncogenic c-RAF kinase (c-RAF-1-BxB) transgene in these cells. Taken together, these findings suggest that DACE is a promising lead compound for the development of an anti-lung-cancer drug.

No abstract

C 4 -Symmetrical dirhodium(II) tetracarboxylates are highly efficient catalysts for the asymmetric intermolecular aziridination of substituted alkenes with sulfamates. The reaction proceeds with high levels of efficiency and chemoselectivity to afford aziridines with excellent yields of up to 95% and enantiomeric excesses of up to 99%. The scope of the alkene aziridination includes mono-, di-, and trisubstituted olefins as well as the late-stage functionalization of complex substrates. The reaction can be performed on a gram-scale with a catalyst loading of 0.1 mol %. Our DFT study led us to propose a two-spin-state mechanism, involving a triplet Rh−nitrene species as key intermediate to drive the stereocontrolled approach and activation of the substrate.

Nonsmall cell lung cancer (NSCLC) represents an important cause of mortality worldwide due to its aggressiveness and growing resistance to currently available therapy. Cucurbitacins have emerged as novel potential anticancer agents showing strong antiproliferative effects and can be promising candidates for combined treatments with clinically used anticancer agents. This study investigates the synergistic antiproliferative effects of a new semisynthetic derivative of cucurbitacin B (DACE) with three chemotherapy drugs: cisplatin (CIS), irinotecan (IRI), and paclitaxel (PAC) on A549 cells. The most effective combinations were selected for studies of the mechanism of action. Using an in silico tool, DACE seems to act by a different mechanism of action when compared with that of different classes of drugs already used in clinical settings. DACE also showed potent synergic effects with drugs, and the most potent combinations induced G2/M cell cycle arrest by modulating survivin and p53 expression, disruption of F-actin cytoskeleton, and cell death by apoptosis. These treatments completely inhibited the clonogenic potential and did not reduce the proliferation of nontumoral lung cells (MRC-5). DACE also showed relevant antimigratory and anti-invasive effects, and combined treatments modulated cell migration signaling pathways evolved with metastasis progression. The effects of DACE associated with drugs was potentiated by the oxidant agent l-buthionine-sulfoximine (BSO), and attenuated by N-acetilcysteine (NAC), an antioxidant agent. The antiproliferative effects induced by combined treatments were attenuated by a pan-caspase inhibitor, indicating that the effects of these treatments are dependent on caspase activity. Our data highlight the therapeutic potential of DACE used in combination with known chemotherapy drugs and offer important insights for the development of more effective and selective therapies against lung cancer.