620932-73-2Relevant academic research and scientific papers
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.
Asymmetrie aldol reaction of acetaldehyde and isatin derivatives for the total syntheses of ent-convolutamydine e and cpc-1 and a half fragment of madindoline A and B
Itoh, Takahiko,Ishikawa, Hayato,Hayashi, Yujiro
supporting information; experimental part, p. 3854 - 3857 (2009/12/05)
The asymmetric aldol reaction of isatin derivatives and acetaldehyde has been developed using 4-hydroxydiarylprolinol as a catalyst, affording the aldol products with high enantioselectivity, these products being key intermediates in the synthesis of 3-hy
SELECTIVELY DELIVERABLE ISATIN-BASED CYTOTOXIC AGENTS
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Page/Page column 41, (2008/12/06)
The invention relates to compounds comprising a cytotoxic isatin derivative conjugated to a cell targeting moiety via a spacer group. These conjugates allow the cytotoxic isatin derivaties to be targeted to particular cell and tissue types. The invention
An investigation into the cytotoxicity and mode of action of some novel N-alkyl-substituted isatins
Vine, Kara L.,Locke, Julie M.,Ranson, Marie,Pyne, Stephen G.,Bremner, John B.
, p. 5109 - 5117 (2008/03/13)
A range of substituted N-alkylisatins were synthesized and their cytotoxicity evaluated against several cancer cell lines in vitro. SAR studies indicated that the introduction of an aromatic ring with a one or three carbon atom linker at N1 enhanced the activity from that of the allyl, 2′-methoxyethyl, and 3′-methylbutyl N-substituted isatins. Furthermore, electron-withdrawing groups substituted at the meta or para position of the ring were favored over the ortho orientation. Of the 24 compounds screened, nine displayed sub-micromolar IC50 values and in general demonstrated greater selectivity toward leukemia and lymphoma cell lines over any of the carcinoma cell lines tested. 5,7-Dibromo-N-(p-methylbenzyl) isatin (6) was the most active compound, inhibiting the metabolic activity of both U937 and Jurkat cancer cell lines at 0.49 μM. Various N-alkylisatins were also found to dramatically alter lymphocyte morphology, destabilize microtubules, inhibit tubulin polymerization, induce G2/M cell cycle arrest, and activate the effector caspase-3 and -7.
