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Bioorg Med Chem Lett ; 28(14): 2485-2489, 2018 08 01.
Article in English | MEDLINE | ID: mdl-29880399

ABSTRACT

In this article we present a series of non-cytotoxic potent human choline kinase (CK) inhibitors that exhibit nanomolar antiplasmodial activity in vitro. The most active antiplasmodial compounds, 10a-b, bearing a pyridinium cationic head were inactive against CK, while compounds 10g and 10j with a quinolinium moiety exhibit moderate inhibition of both the parasite and the enzyme. The results point towards an additional mechanism of action unrelated to CK inhibition that remains to be established.


Subject(s)
Antimalarials/pharmacology , Biphenyl Compounds/pharmacology , Choline Kinase/antagonists & inhibitors , Ethane/analogs & derivatives , Plasmodium falciparum/drug effects , Protein Kinase Inhibitors/pharmacology , Antimalarials/chemical synthesis , Antimalarials/chemistry , Biphenyl Compounds/chemical synthesis , Biphenyl Compounds/chemistry , Choline Kinase/metabolism , Dose-Response Relationship, Drug , Ethane/chemical synthesis , Ethane/chemistry , Ethane/pharmacology , Humans , Molecular Structure , Parasitic Sensitivity Tests , Plasmodium falciparum/metabolism , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Salts/chemical synthesis , Salts/chemistry , Salts/pharmacology , Structure-Activity Relationship
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