Biotransformation of 1α,11α-dihydroxyisopimara-8(14),15-diene by Cunninghamella echinulata NRRL 1386 and their neuroprotective activity.

The isopimarane diterpene, 1α,11α-dihydroxyisopimara-8(14),15-diene (1), is the major constituents from the rhizomes of Kaempferia marginata (Zingiberaceae), a Thai medicinal plant. The microbial transformation of parent compound 1 by the fungus Cunninghamella echinulata NRRL 1386 gave five new metabolites, 7α,11α-dihydroxy-1-oxoisopimara-8(14),15-diene (2), 3ß,7α,11α-trihydroxy-1-oxoisopimara-8(14),15-diene (3), 7ß,11α-dihydroxy-1-oxoisopimara-8(14),15-diene (4), 7α-hydroxy-1,11-dioxoisopimara-8(14),15-diene (5) and 1α,7ß,11α-trihydroxyisopimara-8(14),15-diene (6), together with three known metabolites, 7-9. The structures of the new metabolites were elucidated by spectroscopic techniques. The known compounds were identified by comparison of the spectroscopic and physical data with those of reported values. The parent compound 1 and the metabolites have been neuroprotective activities evaluated against Aß25-35-induced damage in human neuroblastoma cells (SK-N-SH). Among them, compounds 1-3, 5 and 7-9 had significant neuroprotective activities at a concentration of 2.5 µM. The results demonstrated that these compounds might be worth for further development into therapeutic agents for the treatment of neurodegenerative diseases.

Microbial transformation of isocoronarin D by Cunninghamella echinulata NRRL 1386.

The diterpene isocoronarin D (1) is a bioactive major constituent of labdane diterpene from the aerial parts of Curcuma comosa Roxb. (Zingiberaceae), the Thai medicinal plant. Microbial transformation of 1 was performed by the fungus Cunninghamella echinulata NRRL 1386 to yield three new metabolites, 3ß-hydroxyisocoronarin D (2), 6α-hydroxyisocoronarin D (3) and 3ß,7α-dihydroxyisocoronarin D (4). The structures of the new compounds were elucidated by spectroscopic techniques.

Control of aflatoxigenic strains by Cinnamomum porrectum essential oil.

Essential oil from the bark of Cinnamomum porrectum (Roxb.) Kosterm was obtained by hydrodistillation using a Clevenger-type system for 3 h and identified by gas chromatography-mass spectrometry. The compounds were safrole (93.9%), elemicine (4.3%) and methyl eugenol (1.7%). The effect of essential oil on mycelial growth, sporulation, and aflatoxin B1 production of Aspergillus parasiticus IMI 283883 and Aspergillus flavus IMI 242684 was evaluated using contact and vapor treatments. Aflatoxin B1 was determined using the Enzyme-linked immunosorbent assay. The results showed that C. porrectum (Roxb.) Kosterm essential oil at concentrations more than 200 ppm exhibited inhibition effect on mycelial growth, sporulation, and aflatoxin B1 production of both Aspergillus strains as compared with control. The fumigation activities via vapor treatment showed higher inhibition than contact treatment. This study suggests that C. porrectum (Roxb.) Kosterm essential oil represents a good alternative in eco-friendly control of aflatoxigenic strain on food and agricultural commodities.

Potent vasorelaxant analogs from chemical modification and biotransformation of isosteviol.

Isosteviol (1) has been reported to exhibit moderate vasorelaxant activity. In order to enhance the bioactivity of this compound, chemical modification of 1 to the dihydro analog, ent-16ß-hydroxybeyeran-19-oic acid (2), was undertaken. Compound 2 was then converted to the corresponding acetate derivative, ent-16ß-acetoxybeyeran-19-oic acid (3). Biotransformation of compounds 1-3 by the fungus Cunninghamella echinulata NRRL 1386 was investigated and the metabolites 4-9 were obtained. The substrates and their metabolites were subjected to in vitro rat aorta relaxant activity evaluation. The metabolite 4, ent-7α-hydroxy-16-ketobeyeran-19-oic acid, exhibited the most highly potent activity, with EC50 of 3.46 nM, whereas the parent compound 1 showed relatively low activity (EC50 57.41 nM). A 17-fold increase in vasorelaxant activity of the analog 4 relative to compound 1 is of particular significant. Compound 4 exerted vasorelaxant activity at particularly low concentration and the vasorelaxant profile reached maximum at relatively low concentration, especially when compared with acetylcholine, the positive control.

Biotransformations of 20-hydroxyecdysone and analogues by Curvularia lunata NRRL 2178.

20-Hydroxyecdysone, the arthropod moulting hormone, was biotransformed by the fungus Curvularia lunata NRRL 2178 to the rare ecdysteroid, 2-dehydro-3-epi-20-hydroxyecdysone, and the novel 3alpha,9alpha-cyclo ecdysteroid analogue, (20R,22R)-3beta,14alpha,20,22,25-pentahydroxy-3alpha,9alpha-cyclo-5beta-cholest-7-en-2,6-dione in 14 and 44% yields, respectively. Ponasterone A and pterosterone were similarly biotransformed to the corresponding 2-dehydro-3-epi- and 3alpha,9alpha-cyclo-analogues.