2089-21-6Relevant academic research and scientific papers
Identification, design and biological evaluation of heterocyclic quinolones targeting plasmodium falciparum Type II NADH:Quinone oxidoreductase (PfNDH2)
Leung, Suet C.,Gibbons, Peter,Amewu, Richard,Nixon, Gemma L.,Pidathala, Chandrakala,Hong, W. David,Pacorel, Bénédicte,Berry, Neil G.,Sharma, Raman,Stocks, Paul A.,Srivastava, Abhishek,Shone, Alison E.,Charoensutthivarakul, Sitthivut,Taylor, Lee,Berger, Olivier,Mbekeani, Alison,Hill, Alasdair,Fisher, Nicholas E.,Warman, Ashley J.,Biagini, Giancarlo A.,Ward, Stephen A.,O'Neill, Paul M.
supporting information; experimental part, p. 1844 - 1857 (2012/05/05)
Following a program undertaken to identify hit compounds against NADH:ubiquinone oxidoreductase (PfNDH2), a novel enzyme target within the malaria parasite Plasmodium falciparum, hit to lead optimization led to identification of CK-2-68, a molecule suitab
Flexible estrogen receptor modulators: Design, synthesis, and antagonistic effects in human MCF-7 breast cancer cells
Meegan,Hughes,Lloyd,Williams,Zisterer
, p. 1072 - 1084 (2007/10/03)
Although many series of estrogen receptor antagonists continue to be produced, the majority are direct structural analogues of existing modulators. To examine the tolerance of the estrogen receptor toward flexible ligands, a series of novel flexible estrogen receptor antagonists were prepared and their antiproliferative effects on human MCF-7 breast tumor cells investigated. Each of these compounds deviated from the traditional triphenylethylene backbone associated with common tamoxifen analogues through the introduction of a flexible methylene (benzylic) spacing group between one of the aryl rings and the ethylene group and through variations in the basic side chain moiety. The compounds prepared, when assayed in conjunction with a tamoxifen standard, demonstrated high potency in antiproliferative assays against an MCF-7 human breast cancer cell line with low cytotoxicity and high binding affinity. A computational study was undertaken to investigate the compounds' potential interactions with specific residues within the human estrogen receptor α ligand-binding domain (ER-LBD), predicting these compounds bind in an antiestrogenic fashion within the ER-LBD and interact with those important residues previously identified in the structures of ER-LBD agonist/antagonist cocrystals. These compounds further illustrate the eclectic nature of the estrogen receptor in terms of ligand flexibility tolerance.
