Discovery of Anticancer Agents of Diverse Natural Origin.

Research progress from mainly over the last five years is described for a multidisciplinary collaborative program project directed toward the discovery of potential anticancer agents from a broad range of taxonomically defined organisms. Selected lead compounds with potential as new antitumor agents that are representative of considerable structural diversity have continued to be obtained from each of tropical plants, terrestrial and aquatic cyanobacteria, and filamentous fungi. Recently, a new focus has been on the investigation of the constituents of U.

Update on Phytochemical and Biological Studies on Rocaglate Derivatives from Aglaia Species.

With about 120 species, is one of the largest genera of the plant family Meliaceae (the mahogany plants). It is native to the tropical rainforests of the Indo-Australian region, ranging from India and Sri Lanka eastward to Polynesia and Micronesia. Various species have been investigated since the 1960s for their phytochemical constituents and biological properties, with the cyclopenta[]benzofurans (rocaglates or flavaglines) being of particular interest.

Anti-HIV diphyllin glycosides from Justicia gendarussa.

In a search for new anti-HIV active leads from over several thousands of plant extracts, we have identified a potent plant lead. The active plant is determined as Justicia gendarussa (Acanthaceae), a medicinal plant that has been used for the treatment of injury, arthritis and rheumatism in Asia including China. Our bioassay-guided fractionation of the methanol extract of the stems and barks of the plant led to the isolation of two anti-HIV compounds, justiprocumins A and B.

Discovery of Bioactive Compounds by the UIC-ICBG Drug Discovery Program in the 18 Years Since 1998.

The International Cooperative Biodiversity Groups (ICBG) Program based at the University of Illinois at Chicago (UIC) is a program aimed to address the interdependent issues of inventory and conservation of biodiversity, drug discovery and sustained economic growth in both developing and developed countries. It is an interdisciplinary program involving the extensive synergies and collaborative efforts of botanists, chemists and biologists in the countries of Vietnam, Laos and the USA. The UIC-ICBG drug discovery efforts over the past 18 years have resulted in the collection of a cumulative total of more than 5500 plant samples (representing more than 2000 species), that were evaluated for their potential biological effects against cancer, HIV, bird flu, tuberculosis and malaria.

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.

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.

Isolation and characterization of minor analogues of silvestrol and other constituents from a large-scale re-collection of Aglaia foveolata.

Two new minor silvestrol analogues [2'''-episilvestrol (1) and 2''',5'''-diepisilvestrol (2)], together with a new 21-norbaccharane-type triterpene (3), two new 3,4-secodammarane triterpenes (4 and 5), and a new eudesmane sesquiterpene (6), as well as nine known compounds, were isolated from a large-scale re-collection of the CHCl(3)-soluble extract of the stem bark of Aglaia foveolata obtained in Kalimantan, Indonesia. The structures of the new compounds were established by interpretation of their spectroscopic data. All of the isolates were tested for cytotoxicity against HT-29 cells.

Estrogenic and serotonergic butenolides from the leaves of Piper hispidum Swingle (Piperaceae).

Ethnopharmacological Relevance: Our previous work has demonstrated that several plants in the Piperaceae family are commonly used by the Q'eqchi Maya of Livingston, Guatemala to treat amenorrhea, dysmenorrhea, and pain. Extracts of Piper hispidum Swingle (Piperaceae), bound to the estrogen (ER) and serotonin (5-HT7) receptors.

Aim Of The Study: To investigate the estrogenic and serotonergic activities of Piper hispidum extracts in functionalized assays, identify the active chemical constituents in the leaf extract, and test these compounds as agonists or antagonists of ER and 5-HT7.

Bioactivity-guided isolation of cytotoxic sesquiterpenes of Rolandra fruticosa.

Cytotoxicity-guided fractionation of a methanol extract of the leaves and twigs of Rolandra fruticosa using the HT-29 human colon cancer cell line led to the isolation of seven sesquiterpene lactones, including the hitherto unknown isorolandrolide, 13-methoxyisorolandrolide (1), and bourbonenolide, 2alpha,13-diacetoxy-4alpha-hydroxy-8alpha-isobutyroyloxybourbonen-12,6alpha-olide (2), as well as five known compounds, 13-acetoxyrolandrolide (3), 8-desacyl-13-acetoxyrolandrolide-8-O-tiglate (4), 2-epi-glaucolide E (5), 2alpha,13-diacetoxy-4alpha-hydroxy-8alpha-methacryloyloxybourbonen-12,6alpha-olide (6), and 2alpha,13-diacetoxy-4alpha-hydroxy-8alpha-tigloyloxybourbonen-12,6alpha-olide (7). The structures of the two sesquiterpenes were elucidated on the basis of spectroscopic methods. All isolates were evaluated for their cytotoxicity using the HT-29 cell line, and only 13-acetoxyrolandrolide (3) was found to possess a potent inhibitory effect against this cell line.

Medical potential of plants used by the Q'eqchi Maya of Livingston, Guatemala for the treatment of women's health complaints.

Investigation on the medical ethnobotany of the Q'eqchi Maya of Livingston, Izabal, Guatemala, was undertaken in order to explore Q'eqchi perceptions, attitudes, and treatment choices related to women's health. Through participant observation and interviews a total of 48 medicinal plants used to treat conditions related to pregnancy, childbirth, menstruation, and menopause were collected and identified followed by the evaluation of 20 species in bioassays relevant to women's health. Results of field interviews indicate that Q'eqchi cultural perceptions affect women's health experiences while laboratory results (estrogen receptor and serotonin receptor binding assays) provide a scientific correlation between empirical medicinal plant use among the Q'eqchi and the pharmacological basis for their administration.

"Studies on biodiversity of Vietnam and Laos" 1998-2005: examining the impact.

The impact of the University of Illinois at Chicago-based Vietnam-Laos International Cooperative Biodiversity Group (ICBG) Program "Studies on Biodiversity of Vietnam and Laos", which has been in operation for the period of 1998-2005, touches on five major areas of endeavor: (a) biodiversity inventory and conservation; (b) studies on medicinal plants; (c) drug discovery and development; (d) economic development; and (e) issues on intellectual property rights and benefit sharing in natural products drug discovery and development. Highlights are presented and the significance is discussed.