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We studied the in vitro development of resistance to ciprofloxacin, trovafloxacin and moxifloxacin in 5 strains of Streptococcus pneumoniaeresistant to penicillin. We detected the great ease of in vitro development of resistance in the case of ciprofloxacin and the much reduced capacity of moxifloxacin to generate resistance (only 1 strain). Trovafloxacin generated resistance, but more slowly than ciprofloxacin. We consider that study of the capacity to generate resistance should be one of the points to consider when deciding on their large-scale use in respiratory infections, but comparative studies between in vitro and in vivo models should be carried out so as to determine the clinical repercussion of these phenomena.

Pyrazolopyridazine 1a was identified in a high-throughput screening carried out by BASF Bioresearch Corp. (Worcester, MA) as a potent inhibitor of CDK1/cyclin B and shown to have selectivity for the CDK family. Analogues of the lead compound have been synthesized and their antitumor activities have been tested. A molecular model of the complex between the lead compound and the CDK2 ATP binding site has been built using a combination of conformational search and automated docking techniques. The stability of the resulting complex has been assessed by molecular dynamics simulations and the experimental results obtained for the synthesized analogues have been rationalized on the basis of the proposed binding mode for compound 1a. As a result of the SAR study, monofuryl 1o has been synthesized and is one of the most active compounds against CDK1 of this series.

A series of quinoline derivatives as aza analogues of the naphthalene chromophore and a series of “nonfused” tricyclic aromatic systems, in particular 5-arylquinolines and 5- or 6-aryl and heteroaryl naphthalene systems, were synthesized and evaluated for growth-inhibitory properties in several human cell lines. The analysis of quantitative structure−antitumor activity relationships for the growth-inhibitory properties is also reported. Findings suggest that these compounds may not express their cytotoxicity via interaction on DNA.

A series of mono and bisintercalators based on the 5,8-dihydrobenz[de]imidazo[4,5-g]isoquinoline-4,6-dione system were synthesized and evaluated for growth inhibitory properties in several human cell lines. All target compounds showed activity in the micromolar range. Representative compounds were evaluated using UV−vis spectroscopy and viscosimetric determinations, showing that they behave as DNA intercalators. Molecular modeling techniques were used in order to rationalize the moderate activity observed for bisnaphthalimides.

ABSTRACTOf the several microsporidia that infect humans,Enterocytozoon bieneusiis known to cause a gastrointestinal disease whereas Encephalitozoon intestinaliscauses both a disseminated and an intestinal disease. Although several different staining techniques, including the chromotrope technique and its modifications, Uvitex 2B, and the quick-hot Gram-chromotrope procedure, detect microsporidian spores in fecal smears and other clinical samples, they do not identify the species of microsporidia. A need for an easily performed test therefore exists. We reevaluated 120 stool samples that had been found positive for microsporidia previously, using the quick-hot Gram-chromotrope technique, and segregated them into two groups on the basis of spore size. We also screened the smears by immunofluorescence microscopy, using a polyclonal rabbit anti-E. intestinalisserum at a dilution of 1:400. Spores in 29 (24.1%) of the 120 samples fluoresced brightly, indicating that they were E. intestinalisspores. No intense background or cross-reactivity with bacteria, yeasts, or other structures in the stool samples was seen. Additionally, the numbers of spores that fluoresced in seven of these samples were substantially smaller than the numbers of spores that were present in the stained smears, indicating that these samples were probably derived from patients with mixed infections of Enterocytozoon bieneusiand E. intestinalis. Because a 1:400 dilution of this serum does not react with culture-grown Encephalitozoon hellem,Encephalitozoon cuniculi, or Vittaforma corneaeor with Enterocytozoon bieneusispores in feces, we concluded that an immunofluorescence test using this serum is a good alternative for the specific identification of E. intestinalisinfections.