203192-01-2Relevant academic research and scientific papers
Quantitative structure-activity relationships for a series of symmetrical bisquaternary anticancer compounds
Campos, Joaquin M.,Nuez, Maria C.,Sanchez, Rosario M.,Gomez-Vidal, Jose A.,Rodriguez-Gonzalez, Agustin,Baez, Monica,Gallo, Miguel A.,Lacal, Juan Carlos,Espinosa
, p. 2215 - 2231 (2002)
56 biscationic dibromides with distinct polar heads [bis(4-substituted)pyridinium, bis(4-aminoquinolinium), bisquinolinium, and bisisoquinolinium moieties] and several spacers between the two charged nitrogen atoms were synthesised. This oriented synthesis produced 45 inhibitors of choline kinase with antitumour activity against the HT-29 cell line. In an attempt to understand the antiproliferative activity, a quantitative structure-activity relationship was developed. The unknown σR and σR+ descriptors for the diallylamino, pyrrolidino, piperidino and perhydroazepino groups and σR for the N-methylanilino moiety, were estimated by 13C NMR spectroscopy in a simple, fast and reproducible manner. The electron characteristic of the substituent at position 4 of the heterocycle and the theoretical lipophilic character of the whole molecule were found to significantly affect the antitumour activity. 1,1′-[Ethylenebis(benzene-1,4-diylmethylene)]bis[4-(N-methylanilino) pyridinium] dibromide is the most active compound of the series so far described and shows a reasonable agreement between predicted and observed antiproliferative data (predicted pIC50=6.50, experimental pIC50=6.46).
DIAGNOSING AND TREATING CANCER
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Paragraph 00190, (2014/10/18)
The invention relates to compositions and methods for diagnosing as well as treating cancer diseases associated with choline kinase (ChoK). Specifically, the invention relates to a composition comprising an intrinsically fluorescent choline kinase (ChoK)
Homodimeric bis-quaternary heterocyclic ammonium salts as potent acetyl- and butyrylcholinesterase inhibitors: A systematic investigation of the influence of linker and cationic heads over affinity and selectivity
Conejo-García, Ana,Pisani, Leonardo,Del Carmen Nú?ez, Maria,Catto, Marco,Nicolotti, Orazio,Leonetti, Francesco,Campos, Joaquín M.,Gallo, Miguel A.,Espinosa, Antonio,Carotti, Angelo
experimental part, p. 2627 - 2645 (2011/06/21)
A molecular library of quaternary ammonium salts (QASs), mainly composed of symmetrical bis-quaternary heterocyclic bromides exhibiting choline kinase (ChoK) inhibitory activity, were evaluated for their ability to inhibit acetyl- and butyrylcholinesterase (AChE and BChE, respectively). The molecular framework of QASs consisted of two positively charged heteroaromatic (pyridinium or quinolinium) or sterically hindered aliphatic (quinuclidinium) nitrogen rings kept at an appropriate distance by lipophilic rigid or semirigid linkers. Many homodimeric QASs showed AChE and BChE inhibitory potency in the nanomolar range along with a low enzymatic selectivity. Computational studies on AChE, BChE, and ChoK allowed identification of the key molecular determinants for high affinity and selectivity over either one of the three enzymes and guided the design of a hybrid bis-QAS (56) exhibiting the highest AChE affinity (IC50 = 15 nM) and selectivity over BChE and ChoK (SI = 50 and 562, respectively) and a promising pharmacological potential in myasthenia gravis and neuromuscular blockade.
