Amsha Yasin

Biotransformation of (+)-androst-4-ene-3,17-dione

Fermentation of (+)-androst-4-ene-3,17-dione (1) with Curvularia lunata for 10 days yielded five oxidative and reductive metabolites, androsta-1,4-diene-3,17-dione (2), 17β-hydroxyandrosta-1,4-dien-3-one (3), 11α-hydroxyandrost-4-ene-3,17-dione (4), 11α,17β-dihydroxyandrost-4-en-3-one (5) and 15α-hydroxyandrosta-1,4-dien-17-one (6). The structures of these metabolites were elucidated on the basis of spectroscopic techniques. These microbially transformed products were assayed against the clinically important enzymes, tyrosinase and prolyl endopeptidase.

Microbial transformation of cortisol and prolyl endopeptidase inhibitory activity of its transformed products

Incubation of cortisol (1) with Gibberella fujikuruoi for 12 days yielded an oxidatively cleaved product, 11β-hydroxyandrost-4-en-3,17-dione (2), while incubation with Bacillus subtilis and Rhizopus stolonifer yielded the reduced product, 11β, 17α,20,21-tetrahydroxy-(20S)-pregn-4-en-3-one (3). Other reduced products, 11β, 17α, 21-trihydroxy-5α-pregnan-3, 20-dione (4) and 3β, 11β, 17α, 21-tetrahydroxy-5α-pregnan-20-one (5) were obtained by incubation of compound 1 with Bacillus cerus. The inhibitory activity of compounds 1-5 against prolyl endopeptidase enzyme (PEP) was also assayed. Compounds 2 (IC50 162.8 μM) and 4 (IC50 157 μM) have shown significant inhibitory activity against PEP.

Terminalin A, a novel triterpenoid from Terminalia glaucescens

Terminalin A 1, a new A-seco-triterpene, was isolated from the stem bark of Terminalia glaucescens Planchon. This compound has an unprecedented rearranged seco-glutinane structure with a pyran ring-A and an isopropanol moiety, as determined by spectroscopic and single-crystal X-ray diffraction analysis. Other known triterpenes, friedelin, β-sitosterol, stigmasterol, lupeol, betulinic acid, β-amyrin and long chain fatty acids were also isolated.

Prolyl endopeptidase and thrombin inhibitory diterpenoids from the bark of Xylopia aethiopica.

The inhibitory effects of seven diterpenes, belonging to three different structural classes and isolated from the bark of Xylopia aethiopica, were investigated against the enzymes prolyl endopeptidase (PEP) and α-thrombin. Five compounds exhibited inhibitory activity against them.

Prolyl endopeptidase inhibitors from Syzygium samarangense (Blume) Merr. & L. M. Perry.

Compounds isolated from the hexane extract of the leaves of Syzygium samarangense (Blume) Merr. & L. M. Perry were tested for inhibitory activity against the following serine proteases: trypsin, thrombin and prolyl endopeptidase. The compounds were identified as an intractable mixture of α-carotene and β-carotene (1), lupeol (2), betulin (3), epi-betulinic acid (4), 2′,4′-dihydroxy-6′-methoxy-3′-methylchalcone (5), 2′-hydroxy-4′,6′-dimethoxy-3′- methylchalcone (6), 2′,4′-dihydroxy-6′-methoxy-3′,5v-dimethylchalcone (7), 2′,4′-dihydroxy- 6′-methoxy-3′-methyldihydrochalcone (8) and 7-hydroxy-5-methoxy-6,8-dimethylflavanone (9). Hydrogenation of compounds 5, 6 and 7 yielded compound 8, 2′-hydroxy-4′,6′-dimethoxy- 3′-methyldihydrochalcone (10) and 2′,4′-dihydroxy-6′-methoxy-3′,5-dimethyldihydrochalcone (11), respectively. The hydrogenated products of compounds 6 and 7 were also tested for enzyme inhibitory activity. In addition, β-sitosterol (12) and β-ᴅ-sitosterylglucoside (13) were also isolated. This is the first report of the isolation of compounds 1-6, 8 and 13 from this plant. Compounds 3-8 and 10 exhibited significant and selective inhibition against prolyl endopeptidase among three serine proteases. This is the first report of this kind of activity for all these compounds.

New diterpene isopimara-7,15-dien-19-oic acid and its prolyl endopeptidase inhibitory activity

The ethanolic extract of the bulbs of Fritillaria imperialis was subjected to fractionation by solvent–solvent extraction. The nonpolar fraction showed inhibitory activity against prolyl endopeptidase (PEP) (EC.3.4.21.26), a large intracellular enzyme that preferentially hydrolyze proline-containing oligopeptidase at the carboxylic side of a prolyl residue. We have isolated a diterpenoid isopimara-7,15-dien-19-oic acid (1) from the nonpolar fraction of F. imperialis, and on methylation of compound 1, a methylester 2 was obtained which is a known compound previously isolated from Fritillaria thunbergii. The present article describes the isolation and structural elucidation of isopimara-7,15-dien-19-oic acid (1) by single-crystal X-ray diffraction techniques along with its prolyl endopeptidase inhibitory activity.

New bioactive diterpenoid from Euphorbia decipiens

One new diterpene ester with a tricyclic lathyrane-or myrsinol-type skeleton has been isolated from Euphorbia decipiens Boiss.&Buhse. In addition to one new, the known constituents β-amyrin, β-amyrin acetate, methyl (2,4-dihydroxy-3-formyl-6-methoxy) phenyl ketone (2), and 1,1-bis (2,6-dihydroxy-3-acetyl-4-methoxyphenyl) methane (3) have been isolated from the same source. The structure elucidation of the isolated compounds was based primarily on 1D and 2D-NMR analysis, including COSY, HMQC, HMBC and NOESY correlations. Compound 1 showed inhibitory activity against prolyl endopeptidase, and also analgesic activity