Antileishmanial and Cytotoxic Activity of Some Highly Oxidized Abietane Diterpenoids from the Bald Cypress, Taxodium distichum.

Two new compounds, namely, a para-benzoquinone ring-containing abietane (1) and a para-benzoquinone ring-containing 7,8-seco-abietane (2), and 14 other known highly oxidized abietane diterpenoids (3-16) were isolated from an extract prepared from the cones of Taxodium distichum, collected in central Ohio. The active subfraction from which all compounds isolated in this study were purified was tested in vivo using Leishmania donovani-infected mice and was found to dose-dependently reduce the parasite burden in the murine livers after iv administration of this crude mixture at 5.6 and 11.1 mg/kg. The structures of 1 and 2 were established by detailed 1D- and 2D-NMR experiments, HRESIMS data, and electronic circular dichroism studies. Compounds 3 and 4 were each fully characterized spectroscopically and also isolated from a natural source for the first time. Compounds 2-16 were tested in vitro against L. donovani promastigotes and L. amazonensis intracellular amastigotes. Compound 2 was the most active against L. amazonensis amastigotes (IC50 = 1.4 µM), and 10 was the most potent against L. donovani promastigotes (IC50 = 1.6 µM). These compounds may be suggested for further studies such as in vivo experimentation either alone or in combination with other Taxodium isolates.

In vitro evaluation of potential bitterness-masking terpenoids from the Canada goldenrod (Solidago canadensis).

In a screening of extracts of selected plants native to Ohio against the human bitterness receptor hTAS2R31, a chloroform-soluble extract of the aerial parts of Solidago canadensis (Canada goldenrod) was determined to have hTAS2R31 antagonistic activity and, thus, was fractionated for isolation of potential bitterness-masking agents. One new labdane diterpenoid, solidagol (1), and six known terpenoids, including two labdane diterpenoids (2 and 3), three clerodane diterpenoids (6ß-angeloyloxykolavenic acid, 6ß-tigloyloxykolavenic acid, and crotonic acid), and a triterpenoid (longispinogenin), were isolated. Among these compounds, 3ß-acetoxycopalic acid (2) was found to be the first member of the labdane diterpene class shown to have inhibitory activity against hTAS2R31 activation (IC50 8 µM). A homology model of hTAS2R31 was constructed, and the molecular docking of 2 to this model indicated that this diterpenoid binds well to the active site of hTAS2R31, whereas this was not the case for the closely structurally related compound 3 (sempervirenic acid). The content of 2 in the chloroform-soluble portion of the methanolic extract of S. canadensis was up to 2.24 g/100 g dry weight, as determined by HPLC.

In vitro evaluation of flavonoids from Eriodictyon californicum for antagonist activity against the bitterness receptor hTAS2R31.

The leaves of the native North American plant, Eriodictyon californicum, were once used to mask the bitter taste of pharmaceuticals, an application currently of importance. Ten flavonoids (1-10) were isolated from the leaves of E. californicum, of which the structure and absolute configuration of 6-methoxyhesperetin (8) were assigned for the first time. In addition, the absolute configurations at C-2 were established for 4'-isobutyrylhomoeriodictyol (3) and 6-methoxyhomoeriodictyol (7). Using a cell-based assay, it was determined that the 7-methoxylated flavanones, sakuranetin (2) and 6-methoxysakuranetin (9), and the flavone, jaceosidin (10), are antagonists of hTAS2R31.

The relevance of higher plants in lead compound discovery programs.

Along with compounds from terrestrial microorganisms, the constituents of higher plants have provided a substantial number of the natural product-derived drugs used currently in Western medicine. Interest in the elucidation of new structures of the secondary metabolite constituents of plants has remained high among the natural products community over the first decade of the 21st century, particularly of species that are used in systems of traditional medicine or are utilized as botanical dietary supplements. In this review, progress made in the senior author's laboratory in research work on naturally occurring sweeteners and other taste-modifying substances and on potential anticancer agents from tropical plants will be described.