Synthesis and Anticancer Properties of Oxazepines Related to Azaisoerianin and IsoCoQuines.

In this article, we report the synthesis and biological properties of a series of novel oxazepines related to isoCA-4 having significant antitumor properties. Among them, three oxazepin-9-ol derivatives display a nanomolar or a sub-nanomolar cytotoxicity level against five human cancer cell lines (HCT116, U87, A549, MCF7, and K562). It was demonstrated that the lead compound in this series inhibits tubulin assembly with an IC value of 1 μM and totally arrests the cellular cycle in the G2/M phase at the low concentration of 5 nM in HCT116 and K562 cells.

N,N-bis-heteroaryl methylamines: Potent anti-mitotic and highly cytotoxic agents.

The synthesis and evaluation of a series of N,N-bis-heterocyclic-methylamines 1 as isoazaerianin analogues are described. It was demonstrated that the replacement of the 3,4,5-trimethoxyphenyl A-ring present in CA-4, isoCA-4 and isoazaerianin by a quinoline or a quinazoline ring is possible and often beneficiary for a high level of cytotoxicity. We have also showed that a carbazole or an indole nucleus are very effective as B-rings in this series, leading to anti-cancer drugs 1 having a sub-nanomolar level of cytotoxicity (1a: IC = 70 pM against HCT116 cells).

1,1-Diheterocyclic Ethylenes Derived from Quinaldine and Carbazole as New Tubulin-Polymerization Inhibitors: Synthesis, Metabolism, and Biological Evaluation.

We report the synthesis and metabolic and biological evaluation of a series of 17 novel heterocyclic derivatives of isocombretastatin-A4 (iso-CA-4) and their structure-activity relationships. Among these derivatives, the most active compound, 4f, inhibited the growth of a panel of seven cancer cell lines with an IC in the low nanomolar range. In addition, 4f showed interesting activity against CA-4-resistant colon-carcinoma cells and multidrug-resistant leukemia cells.

Unexpected Oxidative Ring Opening of Electron-Rich 3-Aminobenzofurans into α-Ketoimines Derivatives.

An unexpected ring opening of 3-aminobenzofurans promoted by NaO tBu in hot toluene, leading to a variety of α-ketoimines, is described. In the presence of 3-iodobenzofurans, NaO tBu mediates the 3-aminobenzofurans ring opening via a possible radical pathway without the help of any external radical sources.

Design, synthesis and anticancer properties of IsoCombretaQuinolines as potent tubulin assembly inhibitors.

The synthesis and evaluation of a new series of IsoCombretaQuinolines (IsoCoQuines) 2 with a 2-substituted-quinoline in place of the 3,4,5-trimethoxyphenyl ring present in isoCA-4 and CA-4 are described. Most of these compounds displayed a potent cytotoxic activity (IC < 10 nM) against a panel of five human cancer cell lines and inhibited tubulin assembly at a micromolar level. The most potent analogue 2b, having a 3-hydroxy-4-methoxyphenyl as B-ring, led to cell cycle arrest in G2/M phase.

Selective Metal-Free Deoxygenation of Unsymmetrical 1,2-Dicarbonyl Compounds by Chlorotrimethylsilane and Sodium Iodide.

For the first time, the combination of chlorotrimethylsilane with NaI is used as a selective reducting system toward 1,2-diketones. This combination is successfully evaluated with several unsymmetrically benzil derivatives, which are reduced in good yields and with a total α-regioselectivity at room temperature. Identification of benzoin intermediates is achieved, and a mechanistic radical process is proposed.