Lyonensinols A - C, 24-Norursane-Type Triterpenoids from the Twigs and Leaves of Lyonia doyonensis and Their Potential Anti-inflammatory and PTP1B Inhibitory Activities.

Lyonia doyonensis is a deciduous shrub native to high-altitude regions of Asia. So far, there is no report on any chemical and biological properties of L. doyonensis. An EtOH extract of L. doyonensis twigs and leaves showed inhibitory activities on protein tyrosine phosphatase 1B and lipopolysaccharide-induced inflammation in BV-2 microglial cells. A phytochemical investigation of this extract led to the isolation of a, so far only ambiguously described, 24-norursane-type triterpenoid, now named lyonensinol A (1: ), along with its two new derivatives, lyonensinols B and C (2: and 3: ), and six known triterpenoids (4 - 9: ). Their structures were elucidated by detailed analysis of spectroscopic data. A combination of chemical conversions, electronic circular dichroism, and Mo2(OAc)4-induced electronic circular dichroism was used to confirm their absolute configurations. Lyonensinols B (2: ) and C (3: ) represent the first examples of norursane-type triterpenoids acylated with a p-coumaroyl moiety. The potential anti-inflammatory and protein tyrosine phosphatase 1B inhibitory activities of all the isolates were evaluated. Compounds 3, 7: , and 8: at 10 µM showed potent inhibitory activities on lipopolysaccharide-induced nitric oxide production in BV-2 microglial cells, with nitric oxide levels decreasing to 31.5, 41.9, and 27.1%, respectively, while compounds 3, 4, 7: , and 8: exhibited notable inhibitory activities against protein tyrosine phosphatase 1B, with IC50 values ranging from 1.7 to 18.2 µM. Interestingly, compounds 3: and 8: , bearing a C-3 trans-p-coumaroyl group, showed not only more potent anti-inflammatory effects, but also exhibited stronger protein tyrosine phosphatase 1B inhibition than their respective stereoisomers (2: and 7: ) with a cis-p-coumaroyl group.

Anti-inflammatory and PTP1B inhibitory sesquiterpenoids from the twigs and leaves of Aglaia lawii.

Twelve sesquiterpenoids with seven different carbon skeletons, including four isodaucanes (1-4), an aromadendrane (5), a guaiane (6), a cadalane (7), two eudesmanes (8 and 9), two bisabolanes (10 and 11), and a megastigmane (12), were isolated from the twigs and leaves of Aglaia lawii (Wight) C. J. Saldanha et Ramamorthy. Of these compounds, amouanglienoids A (1) and B (2) are new isodaucane sesquiterpenoids. This is the first report of isodaucanes from the genus Aglaia, and amouanglienoid A (1) represents the first isodaucane containing a Δ7(8) double bond. Their structures were discerned from extensive spectroscopic analyses, single-crystal X-ray diffraction, and comparison of the experimental and calculated ECD data. In in vitro bioassays, compounds 1, 10, and 11 showed potent inhibitory effects against lipopolysaccharide (LPS)-induced inflammation in BV-2 microglial cells, while compound 11 exhibited considerable inhibition of PTP1B with an IC50 value of 16.05 ± 1.09 µM.

Structurally diverse halosesquiterpenoids from the red alga Laurencia composita Yamada.

A phytochemical investigation on the MeOH extract of the red alga Laurencia composita Yamada led to the discovery of six new highly halogenated sesquiterpenoids, including two bisabolane-type sesquiterpenoids (1 and 2), one nerolidol derivative (7), and three chamigrane-type sesquiterpenoids (9, 10, and 18), together with 13 known sesquiterpenoids. Their structures, including relative configuration, were elucidated by extensive spectroscopic analysis, and by comparison with data for related known compounds. The absolute configuration at C-10 of laurecomposin A (1) was determined by the modified Mosher's method. Halonerolidol (7) is the first naturally occurring halogenated nerolidol derivative, while compositacin L (9) represents the third example of chamigranes having a C-10 carbonyl group. Antifungal, antibacterial, and receptor tyrosine kinase inhibitory activities of these isolates were evaluated. The results showed that compounds 1-3 and 5 exhibited significant antifungal activity against Microsporum gypseum (Cmccfmza) with MIC values of 4, 8, 8, and 4 µg/mL, respectively. Additionally, compounds 1-3 and 5 also displayed promising antibacterial activity against Gram-positive bacteria Staphylococcus aureus Newman strain with MIC values ranging from 10.9 to 26.8 µg/mL.

Dictyoptesterols A-C, ∆22-24-oxo cholestane-type sterols with potent PTP1B inhibitory activity from the brown alga Dictyopteris undulata Holmes.

Three new cholestane-type sterols bearing an unusual ∆22-24-oxo side chain, namely, dictyoptesterols A-C (1-3), were isolated from the brown alga Dictyopteris undulata Holmes, together with five known strutural analogues (4-8). Their structures were elucidated on the basis of by extensive spectroscopic analysis. The absolute configurations of the steroidal nuclei of the new compounds were proposed by a comparison of NMR data with those of related known compounds as well as biogenetic considerations. All of the isolates were evaluated in vitro for their potential to inhibit protein tyrosine phosphatase-1B (PTP1B) activity. The results showed that compounds 1-5 exhibited different levels of PTP1B inhibitory activities with IC50 values ranging from 3.03 ±â€¯0.76 to 15.01 ±â€¯2.88 µM. In particular, compounds 3 and 4 showed promising inhibitory effects towards PTP1B with IC50 values of 3.03 ±â€¯0.76 and 3.72 ±â€¯0.40 µM, respectively, when compared to the positive control oleanolic acid (IC50, 2.83 ±â€¯0.39 µM). The chemotaxonomic significance of these isolated ∆22-24-oxo cholestanes has also been discussed.

Bioactive constituents from the green alga Caulerpa racemosa.

Three diterpenoids, including a pair of epimers, racemobutenolids A and B (1 and 2), and 4',5'-dehydrodiodictyonema A (3), an α-tocopheroid, α-tocoxylenoxy (8), and an 28-oxostigmastane steroid, (23E)-3ß-hydroxy-stigmasta-5,23-dien-28-one (11), together with 12 known compounds, were isolated from the green alga Caulerpa racemosa. The structures of the new compounds were elucidated by detailed analysis of spectroscopic data, and by comparison with data for related known compounds. The epimers (1 and 2) are two unusual diterpenoid lactones bearing a ß-methyl-γ-substituted butenolide moiety, and 3 and 8 represent the first naturally occurring natural products with a hematinic acid ester group and 3,5-dimethylphenoxy functionality, respectively. The enzyme inhibitory activities of the isolated compounds were evaluated in vitro against PTP1B and related PTPs (TCPTP, CDC25B, LAR, SHP-1, and SHP-2). Compounds 3, 5, 6, and 9-14 exhibited different levels of PTP1B inhibitory activities with IC50 values ranging from 2.30 to 50.02µM. Of these compounds, 3, 9, and 11 showed the most potent inhibitory activities towards PTP1B with IC50 values of 2.30, 3.85, and 3.80µM, respectively. More importantly, the potent PTP1B inhibitors 3, 9, and 11 also displayed high selectivity over the highly homologous TCPTP and other PTPs. Also, the neuroprotective effects of the isolates against Aß25-35-induced cell damage in SH-SY5Y cells were investigated. Compounds 10, 11, and 14 exhibited significant neuroprotective effects against Aß25-35-induced SH-SY5Y cell damage with 11.31-15.98% increases in cell viability at 10µM. In addition, the cytotoxic activities of the isolated compounds were tested against the human cancer cell lines A-549 and HL-60.

New isoquinolinequinone alkaloids from the South China Sea nudibranch Jorunna funebris and its possible sponge-prey Xestospongia sp.

Two new renieramycin-type bistetrahydroisoquinolinequinone alkaloids, fennebricins A (1) and B (5), and one new isoquinolinequinone alkaloid, N-formyl-1,2-dihydrorenierol (7), were isolated from the skin of the South China Sea nudibranch Jorunna funebris and its possible sponge-prey Xestospongia sp., together with eight known metabolites, including three bistetrahydroisoquinolinequinones (2-4) and five isoquinolinequinones (8-12). Their structures were elucidated by analysis of spectroscopic data including 1D and 2D NMR and high-resolution electrospray ionization mass spectrometry (HRESIMS) and by comparison with data for related known compounds. All the metabolites except for 7 occurred simultaneously in the two animals, supporting recent ecological studies that the nudibranch J. funebris preys on the sponge of the genus Xestospongia.

Racemosins A and B, two novel bisindole alkaloids from the green alga Caulerpa racemosa.

Racemosin A (1), a structurally unique bisindole alkaloid possessing the seco-indolo[3,2-a]carbazole skeleton with two uncommon indolinenone units both conjugated with a methyl propenoate moiety, and its unusual cyclized derivative, racemosin B (2), were isolated from the green alga Caulerpa racemosa, together with the most commonly encountered pigment in the genus Caulerpa, caulerpin (3). Their structures were elucidated by extensive spectroscopic analysis and by comparison with data for related known compounds. A plausible biosynthetic pathway of 1 and 2 was proposed. In a neuro-protective assay, compound 1 significantly attenuated the Aß2(5-35)-induced SH-SY5Y cell damage with a 14.6% increase in cell viability at the concentration of 10µM when compared to epigallocatechin gallate (EGCG, 16.57% increase at 10 µM) as the positive control.

The alternative medicine pawpaw and its acetogenin constituents suppress tumor angiogenesis via the HIF-1/VEGF pathway.

Products that contain twig extracts of pawpaw (Asimina triloba) are widely consumed anticancer alternative medicines. Pawpaw crude extract (CE) and purified acetogenins inhibited hypoxia-inducible factor-1 (HIF-1)-mediated hypoxic signaling pathways in tumor cells. In T47D cells, pawpaw CE and the acetogenins 10-hydroxyglaucanetin (1), annonacin (2), and annonacin A (3) inhibited hypoxia-induced HIF-1 activation with IC(50) values of 0.02 microg/mL, 12 nM, 13 nM, and 31 nM, respectively. This inhibition correlates with the suppression of the hypoxic induction of HIF-1 target genes VEGF and GLUT-1. The induction of secreted VEGF protein represents a key event in hypoxia-induced tumor angiogenesis. Both the extract and the purified acetogenins blocked the angiogenesis-stimulating activity of hypoxic T47D cells in vitro. Pawpaw extract and acetogenins inhibited HIF-1 activation by blocking the hypoxic induction of nuclear HIF-1alpha protein. The inhibition of HIF-1 activation was associated with the suppression of mitochondrial respiration at complex I. Thus, the inhibition of HIF-1 activation and hypoxic tumor angiogenesis constitutes a novel mechanism of action for these anticancer alternative medicines.