Bioactive saponins from Acacia tenuifolia from the suriname rainforest.

Bioassay-guided fractionation of the MeOH extract of Acacia tenuifolia using the engineered yeast strains 1138, 1140, 1353, and Sc7 as the bioassay tool resulted in the isolation of the three new saponins 3, 5, and 6 and the three known saponins 1, 2, and 4. The structures of the new compounds were established on the basis of HRMS, 1D and 2D NMR spectral data on the intact saponins, and GC-MS analyses of the sugars. Compounds 1,2 and 5,6 showed cytotoxicity against mammalian cell lines.

Bioactive saponins from Swartzia schomburgkii from the suriname rainforest.

Bioassay-guided fractionation of the MeOH extract of Swartzia schomburgkii using the engineered yeast strains 1138, 1140, and 1353 as the bioassay tool resulted in the isolation of five active (2, 4-7) and three inactive (1, 3, 8) saponins. Saponins 4 and 6 are previously unreported. The structures of all of the saponins were established based on 1D and 2D NMR spectral analysis, on acid and alkaline hydrolysis followed by TLC and GC-MS, and by comparison with literature data for known compounds. Three of the isolated compounds (4-6) showed weak cytotoxicity against the M-109 cell line.

A new labdane diterpenoid from Renealmia alpinia collected in the Suriname rainforest.

Continuation of a previous study on Renealmia alpinia resulted in the isolation of the new labdane diterpenoid 3, together with two known diterpenoids. The structure of the new diterpenoid was determined by a combination of NMR techniques and HRFABMS.

Synthesis and biological evaluation of analogues of cryptolepine, an alkaloid isolated from the Suriname rainforest.

Bioassay-guided fractionation of an extract of a mixture of Microphilis guyanensis and Genipa americanacollected in the rainforest of Suriname yielded the known alkaloid cryptolepine (2) as the major active compound in a yeast bioassay for potential DNA-damaging agents; the same compound was later reisolated from M. guyanensis. The structure of cryptolepine was identified unambiguously by spectral data and by its total synthesis. Several cryptolepine derivatives (3-29, 32-41) were synthesized based on modifications of the C-2, N-5, N-10, and C-11 positions. Two cryptolepine dimers (30, 31) were also prepared. The structure modifications did not result in compounds with a higher potency than the parent compound cryptolepine in the yeast assay system, although some derivatives did show significant activity. Selected compounds (6, 7, 17, 22, 23, 26, and 27) were also tested for cytotoxicity in mammalian cell culture, and two compounds showed significant cytotoxic activity.

DNA-damaging steroidal alkaloids from Eclipta alba from the suriname rainforest1.

Bioassay-guided fractionation of the MeOH extract of Eclipta alba using three yeast strains (1138, 1140, and 1353) resulted in the isolation of eight bioactive steroidal alkaloids (1-8), six of which are reported for the first time from nature. The major alkaloid was identified as (20S)(25S)-22,26-imino-cholesta-5,22(N)-dien-3beta-ol (verazine, 3), while the new alkaloids were identified as 20-epi-3-dehydroxy-3-oxo-5,6-dihydro-4,5-dehydroverazine (1), ecliptalbine [(20R)-20-pyridyl-cholesta-5-ene-3beta,23-diol] (4), (20R)-4beta-hydroxyverazine (5), 4beta-hydroxyverazine (6), (20R)-25beta-hydroxyverazine (7), and 25beta-hydroxyverazine (8). Ecliptalbine (4), in which the 22,26-imino ring of verazine was replaced by a 3-hydroxypyridine moiety, had comparable bioactivity to verazine in these assays, while a second alkaloid (8) showed good activity against Candida albicans. All the alkaloids showed weak cytotoxicity against the M-109 cell line.

Bioactive labdane diterpenoids from Renealmia alpinia collected in the Suriname rainforest.

The preservation of tropical rainforests is an important goal both for the intrinsic value of their cultural and biological diversity as well as for the well-being of the peoples who make these forests their home. In addition, tropical forests are potential sources of new pharmaceutical products that can only be found by chemical prospecting in Nature's genetically encoded combinatorial library. As part of an effort to integrate biodiversity conservation and drug discovery with economic development, we have initiated a collaborative program to discover potential pharmaceuticals in the rainforest of Suriname. The plant Renealmia alpinia (Zingiberaceae) was selected for investigation based on its ethnomedical use as a febrifuge, but testing in the yeast Sc-7 assay gave a positive response, indicative of cytotoxic activity. Using this bioassay, the two new labdane diterpense, 11-hydroxy-8(17),12(E)-labdadien-15,-16-dial 11,15-hemiacetal (1) and 16-oxo-8(17),12(E)-labdadien-15-oic acid (2), and the known diterpene, 8(17),12(E)-labdadien-15,16-dial (3), have been isolated. Their structures were elucidated by 1D and 2D NMR techniques (DEPT, COSY, HETCOR, HMBC, and NOESY) and IR, UV, and MS spectra, and the absolute stereochemistry of 1 was established by CD spectroscopy and by the formation and NMR analysis of alpha-methoxyphenylacetyl esters. The hemiacetal 1 was cytotoxic to M109 cells, with an IC50 value of 2.6 micrograms/mL.