14338-36-4Relevant articles and documents
Synthesis and hydrolytic evaluation of acid-labile imine-linked cytotoxic isatin model systems
Matesic, Lidia,Locke, Julie M.,Vine, Kara L.,Ranson, Marie,Bremner, John B.,Skropeta, Danielle
experimental part, p. 1771 - 1778 (2011/04/17)
In this study a series of isatin-based, pH-sensitive aryl imine derivatives with differing aromatic substituents and substitution patterns were synthesised and their acid-catalysed hydrolysis evaluated. These derivatives were functionalised at the C3 carbonyl group of a potent N-substituted isatin cytotoxin and were stable at physiological pH but readily cleaved at pH 4.5. Observed rates of hydrolysis for the embedded imine-acid moiety were in the order para-phenylpropionic acid > phenylacetic acid (para > meta) > benzoic acid (meta > para). The ability to fine-tune hydrolysis rates in this way has potential implications for optimising imine linked, tumour targeting cytotoxin-protein conjugates.
N-Phenyl-N′-(2-chloroethyl)ureas (CEUs) as potential antineoplastic agents. Part 3: Role of carbonyl groups in the covalent binding to the colchicine-binding site
Moreau, Emmanuel,Fortin, Sebastien,Lacroix, Jacques,Patenaude, Alexandre,Rousseau, Jean L.C.,C-Gaudreault, Rene
, p. 1206 - 1217 (2008/09/18)
In the course of the development of N-phenyl-N′-(2-chloroethyl)ureas (CEUs) as potential antineoplastic agents, we investigated the effect of carbonylated substituting chains of the aromatic ring of CEU on their covalent binding to the colchicine-binding site (C-BS). In this study, we found that CEU, 5e, 5f, 8e, and 8f substituted by either a methyl ester or a methyl ketyl group at the ω-position exhibited a significant antiproliferative activity on HT-29, M21, and MCF-7 tumor cells. SDS-PAGE assays and cell cycle analysis confirmed that 5e, 5f, 8e, and 8f covalently bind to the C-BS and arrest the cell division in G2/M phase. Surprisingly, the presence of ω-carboxyl, ω-ethyl esters or ω-amides decreased significantly both the antiproliferative activity and the specificity toward β-tubulin.
"Mercaptan-Tail" Porphyrins: Synthetic Analogues for the Active Site of Cytochrome P-450
Collman, James P.,Groh, Susan E.
, p. 1391 - 1403 (2007/10/02)
The synthesis and characterization of a series of tetraarylporphyrins which bear covalently attached alkyl and aryl mercaptans designed to serve as axial ligands are described.The coordination chemistry of the iron(II) complexes of these "mercaptan-tail" porphyrins has been investigated by 1H NMR, IR, and electronic absorption spectroscopy, magnetic circular dichroism, and magnetic susceptibility measurements.Ferrous complexes of the alkyl mercaptan-tail porphyrins appear to remain four-coordinate, intermediate spin (S = 1) in solution.The situation is less clear in the case of appended aryl mercaptans and a "tail-on/tail-off" equilibrium is implicated.In the presence of carbon monoxide, however, binding of thiol trans to CO is observed in both the alkyl and aryl cases.By the addition of an appropriate base, six-coordinate mercaptide-Fe(II)-CO complexes can be generated; these reproduce quite well the characteristic absorption and MCD spectra of cytochrome P-450, suggesting that such compounds are indeed viable models for the active site of cytochrome P-450.
