Bioassay-guided fractionation of the chloroform-soluble extract of the leaves of Vitex negundo led to the isolation of the known flavone vitexicarpin (1), which exhibited broad cytotoxicity in a human cancer cell line panel. In an attempt to increase the cytotoxic potency of 1, a series of acylation reactions was performed on this compound to obtain its methylated (2), acetylated (3), and six new acylated (4-9) derivatives. Compound 9, the previously unreported 5,3'-dihexanoyloxy-3,6,7,4'-tetramethoxyflavone, showed comparative cytotoxic potency to compound 1 and was selected for further evaluation. However, this compound was found to be inactive when evaluated in the in vivo hollow fiber assay with Lu1, KB, and LNCaP cells at the highest dose (40 mg/kg/body weight) tested, and in the in vivo P-388 leukemia model (135 mg/kg), using the ip administration route.

Cytotoxicity-based, bioassay-guided fractionation of the chloroform-soluble extracts of both the roots and leaves of Picramnia latifolia led to the isolation of two new anthrone C-glycosides, picramniosides G (1) and H (2), two new oxanthrone C-glycosides, mayosides D (3) and E (4), and a new benzanthrone natural product, 6,8-dihydroxy-10-methyl-7H-benz[de]anthracen-7-one (5), together with 10 known compounds, 6,8-dihydroxy-4-methyl-7H-benz[de]anthracen-7-one (6), nataloe-emodin (7), chrysophanein, chrysophanol, 1,5-dihydroxy-7-methoxy-3-methylanthraquinone, pulmatin, 7-hydroxycoumarin, 7-hydroxy-6-methoxycoumarin, beta-sitosterol, and beta-sitosterol glucoside. The structures of 1-5 were established by spectroscopic methods, including 1D and 2D NMR, HRMS, and CD data interpretation. The cytotoxic activity of all isolates was evaluated in a small panel of human cancer cell lines. Compound 7 exhibited significant in vitro cytotoxic activity in the tested cell lines, but no significant activity was observed with an in vivo hollow fiber model at doses of 6.25, 12.5, 25, and 50 mg/kg/injection.

A study of Tabebuia ochracea ssp. neochrysantha, a plant traditionally used in the Amazon against malaria, was pursued. Bioactivity was tested in vitro against Plasmodium berghei and Plasmodium falciparum (FcB2 chloroquine-resistant strain). Inhibitory activity was determined by measuring parasite 3 H-hypoxanthine incorporation. Fractionation of the chloroformic extract of P. ochracea (inner stem bark) afforded five furanonaphthoquinones. The highest antimalarial activity against P. berghei was given by a mixture of two compounds which could not be separated, but the isomeric structures of 5-and 8-hydroxy-2-(1'-hydroxy)-ethylnaphtho-[2,3-b]-furan-4,9-dione ( 1 and 2) were determined from spectroscopic data. The 50% inhibitory concentration (IC 50 ) values obtained with the mixture of compounds 1 and 2 were 1.67 ϫ 10 -7 M for P. berghei and 6.77 ϫ 10 -7 for the FcB2 chloroquineresistant strain of P. falciparum. For the former parasite, the IC 50 value for chloroquine was 5 ϫ 10 -8 M. That for P. falciparum was 1.1 ϫ 10 -7 M. These results indicate that the furanonaphthoquinones isolated from T. ochracea are potential antimalarial compounds.

Activity-directed fractionation of the inner stem bark of Tabebuia ochracea ssp. neochrysanta led to the isolation of two new naphtho[2,3-b]furan-4,9-diones, the 5,8-dihydroxy-2-(1′hydroxyethyl) and 2-acetyl-7-methoxy-8-hydroxy derivatives, 1 and 2, together with four known naphthofurandiones.The stem bark of Tabebuia ochracea ssp. neochrysanta (A. Gentry) A. Gentry (Bignoniaceae) has been used for many years by Tukuna indians of the Colombian Amazon as an antimalarial and for its healing action on ulcers. 1,2 This plant is native to tropical America, from El Salvador to northwest of Venezuela and Colombia and known in folk medicine as "To hua ri", "Vero", and "Cañ aguate". Zani et al. 3 isolated -sitosterol, cycloolivil, lapachol, and seven furanonaphthoquinones from the trunkwood of this plant. We found that the chloroform extract of T. ochracea ssp. neochrysanta showed cytotoxicity against melanoma B16 cells and antimalarial activity, in vitro, against strains of Plasmodium berghei. We report in this paper the structure elucidation of two new furanonaphthoquinones, 1 and 2, which were isolated along with the known 2-acetylnaphtho[2,3-b]furan-4,9-dione, 7-methoxy-8-hydroxy-2-(1′-hydroxyethyl)naphtho[2,3-b]furan-4,9-dione, 2-acetyl-7-methoxynaphtho[2,3-b]furan-4,9dione, and 7-methoxy-2-(1′-hydroxyethyl)naphtho[2,3b]furan-4,9-dione.