Synthesis and cytotoxicities of 7-aza rebeccamycin analogues bearing various substituents on the sugar moiety, on the imide nitrogen and on the carbazole framework

The synthesis of a family of rebeccamycin analogues in which one indole unit has been replaced by a 7-azaindole moiety is described. Substitutions have been carried out on the imide nitrogen, on the carbazole framework and on the sugar part. Compounds with a lactam upper heterocycle have also been prepared. The cytotoxicities of the newly synthesized compounds toward four tumor cell lines, one murine leukemia (L1210) and three human tumor cell lines (prostate carcinoma DU145, colon carcinoma HT29, and non-small cell lung carcinoma A549) have been evaluated and compared to those of rebeccamycin and parent non-aza and aza compounds.     

Novel checkpoint 1 inhibitors

Cell cycle ckeckpoints are activated in response to DNA damage. Their role consists in blocking the cell cycle to allow time for DNA repair. The activity of the G1 checkpoint is dependent on the p53 protein. In more than 50% of human tumor cells, the p53 gene is mutated. In the p53 mutated cells, the G1 checkpoint is lacking. In these cells, only the G2 checkpoint, although weaker than in healthy cells, provides cancer cells with the opportunity to repair the DNA after damage. Therefore, combining a G2 checkpoint inhibitor with a DNA damaging agent should force, selectively cancer cells, into a premature and lethal mitosis, due to an accumulation of DNA lesions. Among the regulators of the G2 checkpoint, Checkpoint 1 kinase (Chk1) plays a major role. A widespread interest has been recently devoted to the discovery of Chk1 inhibitors as potential useful compounds to enhance the antitumor efficiency of DNA damaging agents. This review article will summarize: (i) the chemical structures of the novel Chk1 inhibitors reported in the recent patents; (ii) their inhibitory activity towards Chk1; (iii) their effects on tumor cells in combination with DNA damaging agents; and (iv) the in vivo results on animal models.     

Use of monoclonal antibodies for rapid detection of influenza a viras in nasopharyngeal secretions

Two monoclonal antibodies against influenza A virus were assessed for use as diagnostic reagents in an indirect immunofluorescence assay (IFA) of nasopharyngeal secretions. Monoclonal antibody IA-52, directed at an internal antigen, reacted with all influenza A tested. The high stability of this epitope permitted its use in a rapid IFA test, which gave results comparable to those obtained with polyclonal antibodies and viral isolation. The second monoclonal antibody, IA-279 was directed at a surface epitope (hemagglutinin); it reacted with almost all H₃ subtype strains. Positive IFA using these monoclonal antibodies permitted rapid preliminary differentiation between the current two major subtypes of influenza A virus (H₁N₁,H₃N₂).