Synthesis and Antimalarial Activity of Mallatojaponin C and Related Compounds.

The phloroglucinol mallotojaponin C (1) from Mallotus oppositifolius, which was previously shown by us to have both antiplasmodial and cytocidal activities against the malaria parasite Plasmodium falciparum, was synthesized in three steps from 2',4',6'-trihydroxyacetophenone, and various derivatives were synthesized in an attempt to improve the bioactivity of this class of compounds. Two derivatives, the simple prenylated phloroglucinols 12 and 13, were found to have comparable antiplasmodial activities to that of mallotojaponin C.

Antiproliferative Trihydroxyalkylcyclohexenones from Pleiogynium timoriense.

Investigation of a DCM extract of the bark of Pleiogynium timoriense from the former Merck collection of natural product extracts for antiproliferative activity indicated that it was active with an IC50 value of 1.3 µg/mL against the A2780 ovarian cancer cell line. Bioassay-directed fractionation of this extract yielded the three new bioactive trihydroxyalkylcyclohexenones 1-3. Their structures were determined by a combination of spectroscopic and chemical methods. Compounds 1-3 exhibited submicromolar antiproliferative activity against the A2780 human ovarian cancer cell line, with IC50 values of 0.8, 0.7, and 0.8 µM, respectively.

Bioactive oleanane glycosides from Polyscias duplicata from the Madagascar dry forest.

As part of the International Cooperative Biodiversity Group (ICBG) program, in a search for antiproliferative compounds, an ethanol extract of Polyscias duplicata was investigated due to its antiproliferative activity against the A2780 human ovarian cell cancer line (IC50 6 µg/mL). Seven known oleanane glycosides, 3ß-[(α-L-arabinopyranosyl)oxy]-16α-hydroxyolean-12-en-28-oic acid (1, IC50 8 µM), 3ß-[(α-L-arabinopyranosyl)oxy]-16α,23-dihydroxyolean-12-en-18-oic acid (2, IC50 13 µM), 3ß-[(O-ß-D-glucopyranosyl-(t-->3)-α-L-arabinopyranosyl)oxy]-16α-hydroxyolean-12-en-28-oic acid (3, IC50 7 µM), 3ß-[(O-α-L-rhamnopyranosyl-(1-2)-α-L-arabinopyranosyl)oxy]-16α-hydroxyolean-12-en-28-oic acid (4, IC50 2.8 µM), 3ß-[(O-ß-D-glucopyranosyl-(l-->3)-α-L- arabinopyranosyl)oxy]-23-hydroxyolean-12-en-28-oic acid (5, IC50 10 µM), ß-[(O-α-L-rhamnopyranosyl-(-1.2)-α-L-arabinopyranosyl)oxy]-23-hydroxyolean-12-en-28-oic acid (6, IC50 3.4 µM), and 3ß-[(α-L-arabinopyranosyl)oxy]-23-hydroxyolean-12-en-28-oic acid (7, IC50 3.4 µM) were isolated, and their structures determined using spectroscopic methods.

A new bioactive diterpene glycoside from Molinaea retusa from the Madagascar dry forest.

In a continuing collaboration in a search for new antiproliferative compounds in Madagascar as part of an International Cooperative Biodiversity Group (ICBG), an ethanol extract of Molinaea retusa Radlk. (Sapindaceae) was investigated on the basis of its moderate antiproliferative activity against the A2780 human ovarian cancer cell line (IC50 16 microg/mL). One new compound, 2", 3", 4", 6'-de-O-acetylcupacinoside (1, IC50 15.4 microM) and two known compounds, cupacinoside (2, IC50 9.5 microM) and 6-de-O-acetylcupacinoside (3, IC50 10.9 microM), were isolated by bioassay-directed fractionation using liquid-liquid partitioning, column chromatography, and HPLC. Compounds 2 and 3 also had moderate antiplasmodial activities, with IC50 values of 4.0 and 6.4 microM, respectively, against Plasmodium falciparum, Dd2 strain. The structures were determined using spectroscopic methods.