Design, synthesis and preliminary evaluation of a series of histone deacetylase inhibitors carrying a benzodiazepine ring.

A series of new histone deacetylase inhibitors were designed and synthesized based on hybridization between SAHA or oxamflatin and 5-phenyl-1,4-benzodiazepines. The compounds were tested for their enzyme inhibitory activity on HeLa nuclear extracts, and on human recombinant HDAC1 and HDAC6. Antiproliferative activity was tested on different cancer cells types, while proapoptotic activity was primarily tested on NB4 cells. The compounds showed IC50 values similar to those of SAHA. Compound (S)-8 displayed interesting activity against hematological and solid malignancies.

[Study of primary resistance to antitubercular drugs in Galicia]. / Estudio de las resistencias primarias a fármacos antituberculosos en Galicia.

The primary resistance of 100 specimens of Mycobacterium tuberculosis isolated in patients with active tuberculosis confirmed bacteriologically was studied prospectively over a period of 15 months. Strains resistant to 1 or more drugs were found in 5 patients. Three patients presented resistance to 2 drugs (isoniazide and streptomycin in 2 and rifampicin and isoniazid, streptomycin and ethambutol); and the fifth was resistant only to pyrazinamide. Owing to the few instances of primary resistance found, it was impossible to establish whether any of the factors analyzed in each patient was related to a higher index of resistance, although 4 of the 5 resistant strains came from respiratory specimens. We conclude that the index of primary resistance in our area is low and this allows us to do without prescribing a fourth drug in the first two months of anti-tuberculosis therapy, and makes routine sensitivity tests unnecessary for patients with no history of prior treatment for tuberculosis.