10.1016/j.bmc.2008.11.032
The research focuses on the identification, synthesis, and evaluation of selective small molecule inhibitors targeting human arylamine N-acetyltransferase 1 (NAT1) and its murine homologue, mouse arylamine N-acetyltransferase 2 (Nat2), which are potential markers for breast cancer. The study involves high-throughput screening of a 5000-member compound library against a panel of five different recombinant NAT proteins, including both mammalian and non-mammalian enzymes, to identify broad-spectrum inhibitors and those with specificity for individual NAT isoforms. The most potent inhibitors, identified as rhodanine and thiazolidin-2,4-dione derivatives, exhibit submicromolar activity and competitively inhibit both recombinant proteins and human NAT1 in ZR-75 cell lysates. The experiments utilized various assay methods, including the acetylation of arylamines and hydrolysis of AcCoA, to measure enzyme activity and inhibition. Additionally, 1H NMR studies were conducted on purified mouse Nat2 to confirm the binding of inhibitors within the enzyme's active site. The research also encompassed structure-activity relationship (SAR) analysis to optimize inhibitory activity and in silico modeling to predict the binding mode of the inhibitors to the protein. The compounds were further tested for cell-based toxicity to ensure their potential as non-toxic molecular tools for probing the role of human NAT1 and mouse Nat2 in cellular contexts.
10.1016/0223-5234(87)90277-7
The research aimed to synthesize and evaluate the anti-microbial properties of 2-methyl-3-substituted-4(3H)-quinazolinones, a class of quinazolinone derivatives known for their broad spectrum of biological activities, including anti-microbial effects. The study focused on derivatives with a thiazoline or thiazolidinedione moiety at the 3-position, which were hypothesized to exhibit anti-bacterial and anti-fungal activities. The synthesis involved the use of 3-amino-2-methyl-4(3H)-quinazolinone and various alkyl-, aryl-, or aralkylisothiocyanates to form 2-methyl-3-substituted thiocarbamoylamino-4(3H)-quinazolinones, which were then cyclized to form thiazoline and thiazolidinone derivatives. The anti-microbial activity of these compounds was tested against Gram-positive and Gram-negative bacteria. The results were generally discouraging, with most compounds showing little activity, but some, like compounds 5, 8, 10, and 11, exhibited higher activity against Gram-positive bacteria. Notably, compounds 5 and 8 were equipotent, and compounds 11 and 12 were more potent against Bacillus cereus compared to the reference standard, penicillin G. The study concluded that while the majority of the synthesized compounds did not show promising anti-microbial activity, a few specific derivatives demonstrated potential as anti-microbial agents.
10.1016/j.bmcl.2012.01.052
The research is focused on the synthesis and evaluation of a new class of 2-(trifluoromethyl)-6-arylimidazo[2,1-b][1,3,4]thiadiazole derivatives as potential antitubercular agents. The researchers synthesized these compounds using both conventional and microwave-assisted methods, and evaluated their in vitro antitubercular activity against M. tuberculosis H37Rv. The chemicals that played a role in the research include 5-(trifluoromethyl)-1,3,4-thiadiazol-2-amine, various substituted α-haloaryl ketones, thiazolidine-2,4-dione, 2-thioxothiazolidin-4-one (rhodanine), and 2-(4-oxo-2-thioxothiazolidin-3-yl)acetic acid (rhodanine acetic acid). The synthesized compounds were characterized by IR, NMR, mass spectra, and elemental analysis. The study found that several compounds exhibited good antitubercular activity, with some showing promising potential as lead scaffolds for the development of new anti-TB agents.
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