Enone - and chalcone - chloroquinoline hybrid analogues: in silico guided design, synthesis, antiplasmodial activity, in vitro metabolism, and mechanistic studies

Eric Guantai, Kanyile Ncokazi, T Egan, Jiri Gut, Philip J Rosenthal, Ravi Bhamidipati, Anitha Kopinathan, Peter Smith, Kelly Chibale

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Abstract

Analogues of the previously reported antimalarial hybrid compounds 8b and 12 were proposed with the aim of identifying compounds with improved solubility and retained antimalarial potency. In silico characterization predicted improved solubilities of the analogues, particularly at low pH; they retained acceptable predicted permeability properties but were predicted to be susceptible to hepatic metabolism. These analogues were synthesized and found to exhibit notable in vitro antimalarial activity.
Original languageEnglish
Pages (from-to)3637 - 3649
Number of pages13
JournalJournal of Medicinal Chemistry
Volume54
DOIs
Publication statusPublished - 2011

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