Discovery of Farnesoid X Receptor Antagonists Based on a Library of Oleanolic Acid 3-O-Esters through Diverse Substituent Design and Molecular Docking Methods.

The pentacyclic triterpene oleanolic acid (OA, 1) with known farnesoid X receptor (FXR) modulatory activity was modified at its C-3 position to find new FXR-interacting agents. A diverse substitution library of OA derivatives was constructed in silico through a 2D fingerprint similarity cluster strategy. With further docking analysis, four top-scored OA 3-O-ester derivatives were selected for synthesis. The bioassay results indicated that all four compounds 3 inhibited chenodeoxycholic acid (CDCA)-induced FXR transactivation in a concentration-dependent mode. Among them 3b and 3d are more active than the parent compound OA. A molecular simulation study was performed to attempt to explain the structure-activity relationship (SAR) and the antagonistic action. To the best of our knowledge, this is the first report on semi-synthetic pentacyclic triterpenoids with FXR-modulatory activities.

New ursane-type triterpene with NO production suppressing activity from Nauclea officinalis.

Two new ursane-type triterpenes, named as 3ß, 19α, 23, 24-tetrahydroxyurs-12-en-28-oic acid (1) and 2ß, 3ß, 19α, 24-tetrahydroxyurs-12-en-28-oic acid (2), together with two known triterpenoids, 3-oxo-urs-12-ene-27, 28-dioic acid (3) and quinovic acid-3-ß-rhamnopyranoside (4), were isolated from the stems (with barks) of Nauclea officinalis. The structures of 1 and 2 were determined by the combined use of single-crystal X-ray diffraction and spectroscopic data analysis. The inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells were examined, and compound 1 was found to inhibit NO production, with the IC(50) value of 4.8 µM.

Three new antioxidant C-glucosylanthrones from Aloe nobilis.

Three new C-glucosylanthrones, 3'-O-acetyl-5-hydroxylaloin A (2), 2',6'-O-diacetyl-5-hydroxylaloin A (4), and 4',6'-O-diacetyl-5-hydroxylaloin A (5), along with three known compounds, 5-hydroxyaloin A (1), 6'-acetyl-5-hydroxylaloin A (3), and 4-methoxy-6-(2',4'-dihydroxy-6'-methylphenyl)-pyran-2-one (6), were isolated from the leaves of Aloe nobilis, and their structures were elucidated on the basis of spectroscopic evidences. Compounds 1, 2, 4 and 5 showed antioxidant activity with inhibitory rates of 31.0, 34.0, 34.0, and 42.0%, respectively, at 10(-5) M.

Biotransformation of 3-oxo-oleanolic acid by Absidia glauca.

3-Oxo-oleanolic acid (1) was biotransformed in growing cultures of the fungus Absidia glauca, resulting in three novel hydroxylated metabolites, identified as 1ß-hydroxy-3-oxo-olean-11-en-28,13-lactone (2), 1ß,11α-dihydroxy-3-oxo-olean-12-en-28-oic acid (3), and 1ß,11α,21ß-trihydroxy-3-oxo-olean-12-en-28-oic acid (4).

A new triglucosylated naphthalene glycoside from Aloe vera L.

A new triglucosylated naphthalene derivative, named aloveroside A (1), together with two known anthraquinone dimers and two 6-phenyl-2-pyrone derivatives, was isolated from the Aloe vera ethanolic extracts. The structure of 1 was established as 1-(((4-(1-O-beta-D-glucopyranosyl -(1-->4)-beta-D-xylopyranoside)-hydroxymethyl)-1-hydroxy-8-O-alpha-L-rhamnopyranoside)naphthalene-2-yl)-ethanone by means of spectroscopic evidences and chemical methods. All these compounds were tested for their BACE inhibitory activity but no significant activities were found.

Anti-inflammatory and analgesic effects of ethanol and aqueous extracts of Pterocephalus hookeri (C.B. Clarke) Höeck.

AIM OF THE STUDY: This study evaluates the anti-inflammatory and analgesic activities of the ethanol and aqueous extracts of a Tibetan herb Pterocephalus hookeri (C.B. Clarke) Höeck to provide experimental evidence for its traditional use such as cold, flu and rheumatoid arthritis. MATERIALS AND METHODS: Investigations on the analgesic effects of P. hookeri (C.B. Clarke) Höeck were carried out, including hot-plate test and acetic acid-induced writhing. The anti-inflammatory activities were observed by utilizing the following models: carrageenin-induced edema of the hind paw of rats, cotton pellet-induced granuloma formation in rats, acetic acid-induced permeability, and xylene-induced ear edema in mice. The effects of the administration of indomethacin were also studied. RESULTS: It has been shown that the ethanol and aqueous extracts significantly increased the hot-plate pain threshold and reduced acetic acid-induced writhing response in mice. The ethanol and aqueous extracts remarkably inhibited the increase in vascular permeability induced by acetic acid and ear edema induced by xylene. The ethanol extract also significantly decreased the carrageenin-induced rat paw edema perimeter and inhibited the increase of granuloma weight. CONCLUSION: The results show that the ethanol and aqueous extracts have both central and peripheral analgesic activities and as anti-inflammatory effects, supporting the traditional application of this herb in treating various diseases associated with inflammation and pain.

Jacaranone analogs from Senecio scandens.

Bioassay-guided fractionation of the ethanolic extract of Senecio scandens led to the isolation of four new compounds 4, 5, 7, and 8, along with four known jacaranone analogs (1, 2, 3, 6). Their structures were elucidated on the basis of spectral and chemical evidence. Compound 7 was obtained as a tautomeric mixture of alpha/beta-epimer. The cytotoxic activities of these compounds were evaluated. Among these, compounds 5 and 8 showed potent cytotoxicities. The benzoquinone derivative, jacaranone ethyl ester (1), was the major cytotoxic constituent in this plant with IC(50)s at a range of 0.5-1.0 microg/ml against various tumor cell lines. The SAR of these jacaranone analogs (1-8), isolated from S. scandens, was also discussed.

Synthesis and biological activities of high affinity taxane-based fluorescent probes.

Three fluorescent probes 3a,3b, and 4 have been synthesized through conjugation of fluorescein and difluorescein groups to the 7-OH of C-2 modified paclitaxel and cephalomannine derivatives with very high affinity to microtubules. All these probes exhibited potent tubulin assembly promotion and tumor cell killing activities, thus may be useful as tools for the determination of thermodynamic parameters and exploration of ligand-microtubule interactions.

BACE1 (beta-secretase) inhibitory chromone glycosides from Aloe vera and Aloe nobilis.

Four new chromone glycosides allo-aloeresin D (2) , C-2'-decoumaroyl-aloeresin G (8), 2'-O-coumaroyl-(S)-aloesinol (9), 2'-O-[ P-methoxy-(E)-cinnamoyl]-(S)-aloesinol (10) and nine known chromone glycosides ( 1, 3 - 7, 11 - 13) were isolated from two Aloe spp. plants, A. vera and A. nobilis. Among them, 1 and 8 showed significant inhibitory activity against BACE1 (beta-secretase) with IC (50) values of 39.0 and 20.5 x 10 (-6) M, as well as inhibition of Abeta (1-42) production by 7.4 and 12.3 %, respectively, in B103 neuroblastoma cells at 30 ppm. The preliminary structure-activity relationships of ALOE chromone glucosides were also discussed.

[Studies on chemical constituents from herbs of Botrychium lanuginosum].

OBJECTIVE: To study the chemical constituents of Botrychium lanuginosum. METHOD: Various chromatographic techniques were used to isolate and purify the constituents. The structures were elucidated by chemical evidence and spectroscopic methods. RESULT: Ten compounds were isolated from the 95% ethanol extract of the herb of B. lanuginosum and their structures were elucidated as 30-nor-21beta-hopan-22-one (1), beta-sitosterol (2), luteolin (3), thunberginol A (4), apigenin (5), (6'-O-palmitoyl)-sitosterol-3-O-beta-D-glucoside (6), daucosterol (7), 1-O-beta-D-glucopyranosyl-(2S, 3R, 4E, 8Z)-2-[(2R-hydroxy hexadecanoyl) amino]-4, 8-octadecadiene-1, 3-diol (8), luteolin-7-O-glucoside (9), sucrose (10). CONCLUSION: Compounds 1-10 were isolated from this genus for the first time.

[Active constituents from Aloe arborescens as BACE inhibitors].

AIM: To seek for new components as BACE inhibitors from Aloe arborescens. METHODS: The chemical constituents were isolated by chromatographic methods and their structures were elucidated on the basis of spectral analysis. RESULTS: Eight compounds were isolated and their structures identified as 6'-O-isobutyryl aloenin A (1), aloenin A (2), aloe-emodin (3), (E)-2-acetonyl-8-(2'-O-feruloxyl)-beta-D-glucopyranosyl-7-methoxy-5-methyl-chromone (4), 7-O-methylaloeresin A (5), babarloin A (6), elgonica-dimer A (7), and elgonica-dimer B (8), separately. CONCLUSION: Compound 1 is a new compound, and compound 4 was isolated from A. arborescens for the first time. Pharmacological tests indicated that 2, 4, 5 and 6 have moderate inhibitory active on BACE.

Two novel tetrairidoid glucosides from Dipsacus asper.

[reaction: see text] Two new iridoid glucoside tetramers, dipsanosides A (1) and B (2), the first-reported iridoid tetramers with four glucosides, were isolated from Dipsacus asper. Their structures were determined by analysis of 1D and 2D NMR data as well as by comparison with model compounds. Their cytotoxicities were tested, but neither of them showed obvious activity.