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Isolation, Synthesis, and SAR Study of Antiplasmodial Anthraquinones from Kniphofia caulescens
During our ongoing research as part of a collaboration established between Virginia Tech and the Natural Products Discovery Institute (NPDI), a CH2Cl2 extract of Kniphofia caulescens was found to exhibit antiplasmodial activity against a chloroquine resistant strain of Plasmodium falciparum, with an IC50 value of 6 µg/mL. Liquid-liquid partition, LH-20 and silica gel open column chromatography, and C-18 reverse phase HPLC were used to fractionate the crude extract to obtain seven known anthraquinones (1 – 2, 5 – 9) and two new anthraquinones (3 – 4), which displayed modest antiplasmodial activity, with IC50 values of 25.6 ± 3.6 and 8.9 ± 1.2µM, respectively. The structures of the two new compounds were elucidated based on analysis of their 1D and 2D NMR spectra, and mass spectrometric data. Various analogs of 3 and 4 were prepared to evaluate structure-activity relationships, and one analogue of compound 4, a caffeic acid derivative of aloe emodin, showed good activity, with an IC50 value of 1.3 ± 0.2µM against P. falciparum.