PubMed · 13012244
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M LALLEMAND. 1952. [PAS given intravenously].. https://pubmed.ncbi.nlm.nih.gov/13012244/
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Arylamine N-acetyltransferase (NAT) enzymes catalyze the addition of an acetyl group from acetyl-CoA to a terminal nitrogen on a suitable substrate such as environmentally relevant compounds and pharmaceuticals. In human, there are two highly polymorphic active allozymes, NAT1 and -2, and one inactive pseudogene, NATP. The expression of these enzymes is tissue-specific such that NAT1 is ubiquitously expressed and NAT2 is confined mainly to liver and colorectal tissues. We hypothesized that these genes would be tissue-specifically transcriptionally regulated, and so we isolated putative proximal control regions for both the NAT genes, which were inserted into luciferase vectors and transiently transfected into human liver and bladder cells. The transfected cells were dosed with 4-aminosalicylic acid, sulfamethazine or solvent and the resulting luciferase activity was measured. We found that both NAT1 and -2 regions were inducible in liver cells by both xenobiotics but only one of the NAT1 regions was inducible again by both xenobiotics in bladder cells. These results suggest that the NAT genes may be tissue-specifically transcriptionally regulated.
FT-IR, FT-Raman and FT-SERS spectra of 4-aminosalicylic acid sodium salt dihydrate (4ASAS) have been recorded and analysed. The vibrational bands due to NH2, OH, carboxyl group, and the benzene ring are identified. The CX ipb(17a, 17b), CC ipb(6,18a) and CH ipb (3,14a, 14b) bands are more enhanced in SERS. Broadening of the inplane carboxyl bend indicates interaction with the silver surface. Further the vC=O, v(C-O)c and v(C-O)h are intense in the SERS spectrum. The rocking and wagging modes of NH2 also show up in SERS. The molecule (O, N donor ligand) is thought to adsorb through the carboxyl oxygen atom with the benzene ring in a 'perpendicular side on orientation' with respect to the silver surface.
The activities of six derivatives of a new class of isonicotinoylhydrazones were investigated in vitro against Mycobacterium tuberculosis H37Rv ATCC 27294, isoniazid-resistant M. tuberculosis ATCC 35822, rifampicin-resistant ATCC 35838, pyrazinamide-resistant ATCC 35828, streptomycin-resistant ATCC 35820 and 16 clinical isolates of M. tuberculosis. Several compounds showed interesting antimycobacterial activity against both ATCC strains and clinical isolates, but were less active against isoniazid-resistant M. tuberculosis. Combinations of five isonicotinoylhydrazone derivatives and rifampicin, ethambutol, para-aminosalicylic acid, isoniazid and clofazimine were also investigated against M. tuberculosis H37Rv ATCC 27294 and against ATCC drug-resistant strains. Addition of sub-MICs of some isonicotinoylhydrazone derivatives resulted in a four- to 16-fold reduction in MICs of ethambutol, para-aminosalicylic acid and rifampicin with fractional inhibitory concentrations (FICs) ranging between 0.17 and 0.37, suggesting a synergic interaction against M. tuberculosis H37Rv. Increased activity was also observed with other combinations (FICs 0.53-0.75), including isoniazid, and a synergic interaction between one of the isonicotinoylhydrazone derivatives and isoniazid (FIC 0.26) was shown against isoniazid-resistant M. tuberculosis ATCC 35822, whereas no effects were observed on combining the isonicotinoylhydrazones with clofazimine. The ability of isonicotinoylhydrazones to inhibit specifically the growth of M. tuberculosis, the high selectivity index and their ability to enhance the activity of standard antituberculous drugs in vitro indicate that they may serve as promising lead compounds for future drug development for the treatment of M. tuberculosis infections.