Chemical constituents and biological activities of the fruits of Knema pachycarpa de Wilde.

The n-hexane extract of Knema pachycarpa fruits (Myristicaceae family), exhibiting strong anti-acetylcholinesterase activity, was investigated by gas chromatography/mass spectrometry and then purified by column chromatography. Guided by GC/MS profiling and bioassay, chromatographic separations led to the isolation of five new compounds: two anacardic acid derivatives 1-2, two cardanol derivatives 3-4 and a cardol derivative 5, along with mixtures of known phenolic lipids 6-9. The chemical structures were determined by various spectroscopic methods. New isolated compounds 1-5 were evaluated for their cytotoxicity and anti-acetylcholinesterase activity. Cardanol 3 and cardol 5 were the most active compounds in the acetylcholinesterase inhibitory assay with IC50 values of 2.60 ± 0.24 µM and 2.46 ± 0.23 µM, respectively. Cardanol 4 and cardol 5 showed moderate cytotoxicity against Hela and MCF-7 cancer cell lines with IC50 values ranging from 31.36 ± 0.41 µM to 41.30 ± 2.49 µM.

Litsea Species as Potential Antiviral Plant Sources.

Litsea verticillata Hance (Lauraceae), a Chinese medicine used to treat swelling caused by injury or by snake bites, was the first plant identified by our National Institutes of Health (NIH)-funded International Cooperative Biodiversity Group (ICBG) project to exhibit anti-HIV activities. From this plant, we discovered a class of 8 novel litseane compounds, prototypic sesquiterpenes, all of which demonstrated anti-HIV activities. In subsequent studies, 26 additional compounds of different structural types were identified. During our continuing investigation of this plant species, we identified two new litseanes, litseaverticillols L and M, and a new sesquiterpene butenolide, litseasesquibutenolide. Litseaverticillols L and M were found to inhibit HIV-1 replication, with an IC[Formula: see text] value of 49.6[Formula: see text][Formula: see text]M. To further determine the antiviral properties of this plant, several relatively abundant isolates, including a litseane compound, two eudesmane sesquiterpenes and three lignans, were evaluated against an additional 21 viral targets. Lignans 8 and 9 were shown to be active against the Epstein-Barr Virus (EBV), with EC[Formula: see text] values of 22.0[Formula: see text][Formula: see text]M ([Formula: see text]) and 16.2[Formula: see text][Formula: see text]M ([Formula: see text]), respectively. Since many antiviral compounds have been discovered in L. verticillata, we further prepared 38 plant extracts made from the different plant parts of 9 additional Litsea species. These extracts were evaluated for their anti-HIV and cytotoxic activities, and four of the extracts, which ranged across three different species, displayed 97-100% inhibitory effects against HIV replication without showing cytotoxicity to a panel of human cell lines at a concentration of 20 µg/mL.

Bioassay-Guided Isolation and Structural Modification of the Anti-TB Resorcinols from Ardisia gigantifolia.

Tuberculosis (TB) is a highly contagious disease mainly caused by Mycobacterium tuberculosis H37 RV . Antitubercular (anti-TB) bioassay-guided isolation of the CHCl3 extract of the leaves and stems of the medicinal plant Ardisia gigantifolia led to the isolation of two anti-TB 5-alkylresorcinols, 5-(8Z-heptadecenyl) resorcinol (1) and 5-(8Z-pentadecenyl) resorcinol (2). We further synthesized 15 derivatives based on these two natural products. These compounds (natural and synthetic) were evaluated for their anti-TB activity against Mycobacterium tuberculosis H37 RV . Resorcinols 1 and 2 exhibited anti-TB activity with MIC values at 34.4 and 79.2 µm in MABA assay, respectively, and 91.7 and 168.3 µm in LORA assay, respectively. Among these derivatives, compound 8 was found to show improved anti-TB activity than its synthetic precursor (2) with MIC values at 42.0 µm in MABA assay and 100.2 µm in LORA assay. The active compounds should be regarded as new hits for further study as a novel class of anti-TB agents. The distinct structure-activity correlations of the parent compound were elucidated based on these derivatives.

Anti-tuberculosis constituents from the stem bark of Micromelum hirsutum.

Anti-TB bioassay-directed fractionation led to the isolation of six carbazole alkaloids, as well as the gamma-lactone derivative of oleic acid, from the CH (2)Cl (2) extract of the stem bark of Micromelum hirsutum. The carbazoles include the new micromeline ( 2) and five known alkaloids: lansine ( 3), 3-methylcarbazole ( 4), methyl carbazole-3-carboxylate ( 5), 3-formylcarbazole ( 6), and 3-formyl-6-methoxycarbazole ( 7). Compound 1 was identified as the lactone derivative of oleic acid, (-)- Z-9-octadecene-4-olide, for which the trivial name micromolide ( 1) is suggested. It showed potent in vitro anti-TB activity against H37R v (MIC: 1.5 microg/mL), a selectivity index (SI) of 63, and exhibited activity against the Erdman strain of M. tuberculosis in a J774 mouse macrophage model (EC (90) : 5.6 microg/mL). Thus, 1 appears worthy of further evaluation as a potential new anti-TB agent. Isolates 2, 3, 6 and 7 had anti-TB MIC values between 14.3 and 42.3 microg/mL, while compounds 4 and 5 were considered inactive (MIC > 128 microg/mL). Structure elucidation and identification were based on spectroscopic analysis, including MS, 1D/2D NMR, and a full (1)H spin system analysis of 1.

NMR study of quinolizidine alkaloids: relative configurations, conformations.

Extracts of fruits and leaves of Connarus paniculatus afford six quinolizidine alkaloids which were identified as piptanthine, 18-epipiptanthine, ormosanine, homoormosanine, podopetaline (monohydrochloride) and homopodopetaline on the basis of high-field NMR studies. 1D and 2D NMR experiments provide complete assignments of the (1)H and (13)C spectra. In conjunction with detection of nuclear Overhauser effects (NOESY), these results allow detailed structure characterization including determination of relative configurations for the chiral sites and conformational analysis. Exchange phenomena involving nitrogen inversion were detected.

Cytotoxic flavonoids and alpha-pyrones from Cryptocarya obovata.

One alpha-pyrone, obolactone (1), two chalcones, kurzichalcolactone B (2) and obochalcolactone (3), and two flavanones, oboflavanones A (4) and B (5), have been isolated from the fruits and the trunk bark of Cryptocarya obovata. The structures of the new compounds were elucidated by spectroscopic interpretations. The absolute configuration of obolactone (1) was established by circular dichroism. Obolactone (1) and obochalcolactone (3) display significant activity in in vitro cytotoxic assays against the KB cell line. Biosynthetic pathways for oboflavanones and obochalcolactone are suggested.