6337-67-3Relevant articles and documents
Synthesis and structure-activity analysis of new phosphonium salts with potent activity against African trypanosomes
Taladriz, Andrea,Healy, Alan,Flores Pérez, Eddysson J.,Herrero García, Vanessa,Ríos Martínez, Carlos,Alkhaldi, Abdulsalam A. M.,Eze, Anthonius A.,Kaiser, Marcel,De Koning, Harry P.,Chana, Antonio,Dardonville, Christophe
supporting information; experimental part, p. 2606 - 2622 (2012/06/01)
A series of 73 bisphosphonium salts and 10 monophosphonium salt derivatives were synthesized and tested in vitro against several wild type and resistant lines of Trypanosoma brucei (T. b. rhodesiense STIB900, T. b. brucei strain 427, TbAT1-KO, and TbB48). More than half of the compounds tested showed a submicromolar EC50 against these parasites. The compounds did not display any cross-resistance to existing diamidine therapies, such as pentamidine. In most cases, the compounds displayed a good selectivity index versus human cell lines. None of the known T. b. brucei drug transporters were required for trypanocidal activity, although some of the bisphosphonium compounds inhibited the low affinity pentamidine transporter. It was found that phosphonium drugs act slowly to clear a trypanosome population but that only a short exposure time is needed for irreversible damage to the cells. A comparative molecular field analysis model (CoMFA) was generated to gain insights into the SAR of this class of compounds, identifying key features for trypanocidal activity.
Design, synthesis and characterization of self-assembled As 2L3 and Sb2L3 cryptands
Fontenot, Sean A.,Cangelosi, Virginia M.,Pitt, Melanie A. W.,Sather, Aaron C.,Zakharov, Lev N.,Berryman, Orion B.,Johnson, Darren W.
supporting information; experimental part, p. 12125 - 12131 (2012/03/11)
The syntheses and X-ray crystal structures of six new self-assembled supramolecular As and Sb-containing cryptands are described. Analysis in the context of previously reported As2L3 and Sb 2L3 cryptands reveals that small differences in ligand geometries result in significant differences in the helicity of the complexes and the stereochemistry of the metal coordination within the assembled complexes. Additionally, a new synthetic route is described which involves exposure of reactants to vacuum to help facilitate self-assembly.
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
body text, 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.
