1444512-12-2Relevant academic research and scientific papers
Synthesis and antimalarial activity of N-benzylated (N-arylcarbamoyl)alkylphosphonic acid derivatives
Adeyemi, Christiana M.,Faridoon,Isaacs, Michelle,Mnkandhla, Dumisani,Hoppe, Heinrich C.,Krause, Rui W.M.,Kaye, Perry T.
, p. 6131 - 6138 (2016/12/06)
A series of novel and readily accessible N-benzylated (N-arylcarbamoyl)alkylphosphonate esters and related compounds have been prepared as potential antimalarial agents. Bioassays reveal that some of these compounds exhibit promising activity against Plasmodium falciparum, and exhibit no significant growth inhibition of HeLa cells.
Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors
Bodill, Taryn,Conibear, Anne C.,Mutorwa, Marius K.M.,Goble, Jessica L.,Blatch, Gregory L.,Lobb, Kevin A.,Klein, Rosalyn,Kaye, Perry T.
supporting information, p. 4332 - 4341 (2013/07/27)
DOXP-reductoisomerase (DXR) is a validated target for the development of antimalarial drugs to address the increase in resistant strains of Plasmodium falciparum. Series of aryl- and heteroarylcarbamoylphosphonic acids, their diethyl esters and disodium salts have been prepared as analogues of the potent DXR inhibitor fosmidomycin. The effects of the carboxamide N-substituents and the length of the methylene linker have been explored using in silico docking studies, saturation transfer difference NMR spectroscopy and enzyme inhibition assays using both EcDXR and PfDXR. These studies indicate an optimal linker length of two methylene units and have confirmed the importance of an additional binding pocket in the PfDXR active site. Insights into the constraints of the PfDXR binding site provide additional scope for the rational design of DXR inhibitors with increased ligand-receptor interactions.
