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In this work, we present the first synthesis of dispirooxindole-β-lactams employing optimized methodology of one-pot Staudinger ketene-imine cycloaddition with N-aryl-2-oxo-pyrrolidine-3-carboxylic acids as the ketene source. Spiroconjugation of indoline-2-one with β-lactams ring is considered to be able to provide stabilization and wide scope of functionalization to resulting scaffolds. The dispipooxindoles obtained demonstrated medium cytotoxicity in the MTT test on A549, MCF7, HEK293, and VA13 cell lines, and one of the compounds demonstrated antibacterial activity against E. coli strain LPTD. [ABSTRACT FROM AUTHOR]

A series of novel hydantoin-based dispiroindolinones as potential small-molecule inhibitors of p53–MDM2 protein–protein interaction were synthesized by two methods, using 2-arylidenehydantoins as starting materials. Some compounds demonstrate moderate cytotoxicity against cancer cell lines with IC50 in micromolar concentration range, which is comparable to nutlin-3. Two of the synthesized dispiroindolinones show p53-related activity in p53 reporter activation test. [ABSTRACT FROM AUTHOR]

A series of novel S-, O- and Se-containing dispirooxindole derivatives has been synthesized using 1,3-dipolar cycloaddition reaction of azomethine ylide generated from isatines and sarcosine at the double C=C bond of 5-indolidene-2-chalcogen-imidazolones (chalcogen was oxygen, sulfur or selenium). The cytotoxicity of these dispiro derivatives was evaluated in vitro using different tumor cell lines. Several molecules have demonstrated a considerable cytotoxicity against the panel and showed good selectivity towards colorectal carcinoma HCT116 p53+/+ over HCT116 p53−/− cells. In particular, good results have been obtained for LNCaP prostate cell line. The performed in silico study has revealed MDM2/p53 interaction as one of the possible targets for the synthesized molecules. However, in contrast to selectivity revealed during the cell-based evaluation and the results obtained in computational study, no significant p53 activation using a reporter construction in p53wt A549 cell line was observed in a relevant concentration range. [ABSTRACT FROM AUTHOR]

A novel strain of Actinomycetes was isolated from the body of an ant (Camponotus vagus Scopoli) and its genetic and morphological properties were characterized. The 16S rDNA gene sequence analysis of the isolate revealed its high phylogenetic relationship with type strains of Streptomyces violaceochromogenes NBRC 13100T. As a result of antimicrobial activity assessment, it was found that the fermentation broth of the isolated strain both inhibited the growth and induced the SOS response in E. coli BW25113 ΔtolC strain cells. Using bioassay-guided fractionation, mass spectrometric and NMR analyses we identified the active compound to be nybomycin, a previously described antibiotic. Here we report for the first time Streptomyces producer of nybomycin in association with carpenter ants and demonstrate cytotoxic activity of nybomycin against human cell lines. • Streptomyces sp. isolated from carpenter ants produces antibiotic nybomycin. • Nybomycin demonstrates cytotoxic activity against human cell lines (fibroblasts and lung cancer). • Nybomycin, like fluoroquinolones, induces SOS-response in E.coli cells. [ABSTRACT FROM AUTHOR]

New allobetulin conjugates were obtained through its O-esterification with hex-5-ynoic acid followed by [3+2]-cycloaddition with three azido derivatives of N -acetyl- d -galactosamine. The conjugates are non-toxic in micromolar range against hepatocellular carcinoma cell lines and have a high affinity towards the HO asialoglycoprotein receptor of hepatocytes based on molecular docking and surface plasmon resonance data. [ABSTRACT FROM AUTHOR]

Wehave synthesized and characterized a panel of new binuclearmixed valence Cu(I,II) complexes containing substituted 2-alkylthio-5-arylmethylene-4H-imidazolin-4-ones with unusual structure. These complexesare shown to be cytotoxic for various cell lines. We have found thatthese compounds did not intercalate DNA, inhibited number of polymerases(telomerase predominantly), accumulated in the cell nucleus, and causedDNA degradation. Preliminary studies revealed that lead compound inhibitedhuman breast adenocarcinoma growth in mice model. [ABSTRACT FROM AUTHOR]

Nitrosylsulfuric acid is shown to be a usable reagent for the synthesis of 5-chloroisoxazoles from readily available 1,1-di-chlorocyclopropanes via nitrosation–heterocyclization reaction. A cytotoxicity of some of the prepared 5-chloroisoxazoles towards MCF7, A549, HEK293T and VA13 cell lines was evaluated. [ABSTRACT FROM AUTHOR]