Screening of a small library of natural product extracts derived from endophytic fungi of the Sonoran desert plants in a cell-based anti-HIV assay involving T-cells infected with the HIV-1 virus identified the EtOAc extract of a fermentation broth of Alternaria tenuissima QUE1Se inhabiting the stem tissue of Quercus emoryi as a promising candidate for further investigation. Bioactivity-guided fractionation of this extract led to the isolation and identification of two new metabolites, altertoxins V (1) and VI (2) together with the known compounds, altertoxins I (3), II (4), and III (5). The structures of 1 and 2 were determined by detailed spectroscopic analysis and those of 3-5 were established by comparison with reported data. When tested in our cell-based assay at concentrations insignificantly toxic to T-cells, altertoxins V (1), I (3), II (4), and III (5) completely inhibited replication of the HIV-1 virus at concentrations of 0.50, 2.20, 0.30, and 1.50 μM, respectively. Our findings suggest that the epoxyperylene structural scaffold in altertoxins may be manipulated to produce potent anti-HIV therapeutics.
Most antiretroviral drugs currently in use to treat an HIV-1 infection are chemically synthesized and lead to the development of viral resistance, as well as cause severe toxicities. However, a largely unexplored source for HIV-1 drug discovery is endophytic fungi that live in a symbiotic relationship with plants. These fungi produce biologically active secondary metabolites, which are natural products that are beneficial to the host. We prepared several hundred extracts from endophytic fungi of desert plants and evaluated the inhibitory effects on HIV-1 replication of those extracts that showed less than 30% cytotoxicity in T-lymphocytes. Those extracts that inhibited viral replication were fractionated in order to isolate the compounds responsible for activity. Multiple rounds of fractionation and antiviral evaluation lead to the identification of four compounds, which almost completely impede HIV-1 replication. These studies demonstrate that metabolites from endophytic fungi of desert plants can serve as a viable source for identifying potent inhibitors of HIV-1 replication.
The structure of epi-kokoondiol isolated from the outer root bark of Salacia reticulata var. β-diandra has been elucidated as 21α,26-dihydroxy-D:A-friedo-oleanan-3-one (1) by the application of 2D and NOE difference NMR spectroscopy. Reinvestigation of some KoKoona triterpenoids by NOE difference spectroscopy led to the revision of the structures of kokoondiol, kokoononol, kokzeylanol, kokoonol, and kokzeylanonol as 21β,26-dihydroxy-D:A-friedo-oleanan-3-one (2), 26-hydroxy-D:A-friedo-oleanane-3,21-dione (3), 6β,26-dihydroxy-D:A-friedo-oleanan-3-one (4) 26-hydroxy-D:A-friedo-oleanan-3-one (5), and 6β,26-dihydroxy-D:A-friedo-oleanane-3,21-dione (6), respectively. © 1993.
2-Deacetoxytaxinine B, a taxane diterpenoid, was isolated from the stem bark of Taxus chinensis along with six known taxane diterpenoids and the diterpenolignan, brevitaxin. The structure of 2-deacetoxytaxinine was determined with the aid of spectroscopic techniques, including 2D NMR spectroscopy.
Three new triterpenes zeylanol, zeylanonol and zeylandiol isolated from Kokoona zeylanica have been identified as 6β-hydroxyfriedelan-3-one, 6β-hydroxyfriedelan-3,21-dione and 6β,21β-dihydroxyfriedelan-3-one, respectively by spectroscopic methods and chemical interconversions. © 1979.