Exploration of icariin analog structure space reveals key features driving potent inhibition of human phosphodiesterase-5.

The natural product icariin inhibits human phosphodiesterase-5 (PDE5) and represents a unique pharmacophore for treating erectile dysfunction, pulmonary hypertension, and other diseases. In this study, we explore the available icariin-derived chemical scaffolds through medicinal chemistry to develop novel icariin PDE5 inhibitors with improved potency and specificity. We synthesized six novel semi-synthetic icariin analogs as well as three naturally occurring icariin analogs, and characterized the structure-activity relationship in the context of human PDE5 inhibition using in vitro enzyme inhibition and kinetics assays and molecular modeling.

New phenolic glycosides from .

Two new isobenzofuranone derivatives, polyphthaliside A () and polyphthaliside B (), and a new isocoumarin derivative, polyisocoumarin (), were isolated from . Their structures were elucidated by detailed spectroscopic analysis and chemical methods. The cytotoxicity activity and PTP1B inhibitory activity of compounds 1-3 were estimated and none of them exhibited activities at a concentration of 10 M.

Repeated evolution of cytochrome P450-mediated spiroketal steroid biosynthesis in plants.

Diosgenin is a spiroketal steroidal natural product extracted from plants and used as the single most important precursor for the world steroid hormone industry. The sporadic occurrences of diosgenin in distantly related plants imply possible independent biosynthetic origins. The characteristic 5,6-spiroketal moiety in diosgenin is reminiscent of the spiroketal moiety present in anthelmintic avermectins isolated from actinomycete bacteria.

The molecular structure of plant sporopollenin.

Sporopollenin is a ubiquitous and extremely chemically inert biopolymer that constitutes the outer wall of all land-plant spores and pollen grains. Sporopollenin protects the vulnerable plant gametes against a wide range of environmental assaults, and is considered a prerequisite for the migration of early plants onto land. Despite its importance, the chemical structure of plant sporopollenin has remained elusive.

Abietane diterpenoids from Lycopodium complanatum.

Five new abietane diterpenoids (complanatins A-E, 1-5) have been isolated from the club moss Lycopodium complanatum, along with two known abietane diterpenoids (xanthoperol and sugiol). Their structures were determined by comprehensive analysis of 1D, 2D NMR, CD and HRESIMS data. The cytotoxic effects of five compounds (1-4, 7) were evaluated in three human lung cancer cell lines (MSTO-211H, NCI-H2052 and NCI-H226).

Complete Pathway Elucidation and Heterologous Reconstitution of Rhodiola Salidroside Biosynthesis.

Salidroside is a bioactive tyrosine-derived phenolic natural product found in medicinal plants under the Rhodiola genus. In addition to their anti-fatigue and anti-anoxia roles in traditional medicine, Rhodiola total extract and salidroside have also displayed medicinal properties as anti-cardiovascular diseases and anti-cancer agents. The resulting surge in global demand of Rhodiola plants and salidroside has driven some species close to extinction.

Demystifying traditional herbal medicine with modern approach.

Plants have long been recognized for their therapeutic properties. For centuries, indigenous cultures around the world have used traditional herbal medicine to treat a myriad of maladies. By contrast, the rise of the modern pharmaceutical industry in the past century has been based on exploiting individual active compounds with precise modes of action.

SG2-Type R2R3-MYB Transcription Factor MYB15 Controls Defense-Induced Lignification and Basal Immunity in Arabidopsis.

Lignification of cell wall appositions is a conserved basal defense mechanism in the plant innate immune response. However, the genetic pathway controlling defense-induced lignification remains unknown. Here, we demonstrate the SG2-type R2R3-MYB transcription factor MYB15 as a regulator of defense-induced lignification and basal immunity.

Engineering of Taxadiene Synthase for Improved Selectivity and Yield of a Key Taxol Biosynthetic Intermediate.

Attempts at microbial production of the chemotherapeutic agent Taxol (paclitaxel) have met with limited success, due largely to a pathway bottleneck resulting from poor product selectivity of the first hydroxylation step, catalyzed by taxadien-5a-hydroxylase (CYP725A4). Here, we systematically investigate three methodologies, terpene cyclase engineering, P450 engineering, and hydrolase-enzyme screening to overcome this early pathway selectivity bottleneck. We demonstrate that engineering of Taxadiene Synthase, upstream of the promiscuous oxidation step, acts as a practical method for selectivity improvement.

Sulfoluciferin is Biosynthesized by a Specialized Luciferin Sulfotransferase in Fireflies.

Firefly luciferin is a specialized metabolite restricted to fireflies (family Lampyridae) and other select families of beetles (order Coleoptera). Firefly luciferin undergoes luciferase-catalyzed oxidation to produce light, thereby enabling the luminous mating signals essential for reproductive success in most bioluminescent beetles. Although firefly luciferin and luciferase have become widely used biotechnological tools, questions remain regarding the physiology and biochemistry of firefly bioluminescence.

Involvenflavones A-F, six new flavonoids with 3'-aryl substituent from Selaginella involven.

Six new flavonoids, involvenflavones A-F (1-6), were isolated from Selaginella involven. Their structures were elucidated based on UV, IR, 1D and 2D NMR as well as HR-ESI-MS techniques. All compounds belong to apigenin derivatives with 3'-aryl substituent.

New Selaginellin derivatives from Selaginella tamariscina.

Two new selaginellin derivatives selaginellin P (1) and selaginellin Q (2) were isolated from Selaginella tamariscina. The structures of 1 and 2 were established as 2,4'-dihydroxy-4-methyl-3-[(4-hydroxyphenyl)ethynyl]biphene (1) and 2,4'-dihydroxy-3-[(4-hydroxyphenyl)ethynyl]biphene (2) on the basis of spectroscopic means including HR-ESI-MS, 1D, and 2D NMR experiments.

Neuroprotective naphthalene and flavan derivatives from Polygonum cuspidatum.

Ten naphthalene derivatives including two unusual glycosides possessing a naphthalene-fused piceid via a [C8'-O-C6-C5-C7']-trans-dihydrofuran ring, two flavan derivatives, as well as sixteen known phenolic compounds, were isolated from Polygonum cuspidatum. The structures were determined by extensive NMR, MS, CD data, and chemical evidence. In the in vitro neuroprotective assays, at the concentration of 10 μM, five of these compounds exhibited significant effects against PC12 cells injured by rotenone.

Unciflavones A-F, six novel flavonoids from Selaginella uncinata (Desv.) Spring.

Six new flavonoids, unciflavones A-F (1-6), have been isolated from medicinal plant Selaginella uncinata (Desv.) Spring. Their structures were established on the basis of extensive NMR analysis including 1D NMR ((1)H, (13)C and DEPT) and 2D NMR (COSY, HSQC, HMBC) experiments as well as HRESIMS analysis.

Anticancer potential of Hericium erinaceus extracts against human gastrointestinal cancers.

Ethnopharmacological Relevance: Hericium is a genus of mushrooms (fungus) in the Hericiaceae family. Hericium erinaceus (HE) has been used for the treatment of digestive diseases for over 2000 years in China. HE possesses many beneficial functions such as anticancer, antiulcer, antiinflammation and antimicrobial effects, immunomodulation and other activities.

Increased yield of biotransformation of exemestane with β-cyclodextrin complexation technique.

In this study, 6-methylenandrosta-4-ene-3,17-dione and Hydroxypropyl-β-cyclodextrin (HP-β-CD) were used to form a complex, which could be then biotransformed by Arthrobacter simplex ATCC6946 to obtain the antitumor drug exemestane. The complex was analyzed by UV, DSC and TG techniques, while the products were analyzed by HPLC, NMR and MS. These results confirmed that the β-cyclodextrin not only improved the water-solubility of 6-methylenandrosta-4-ene-3,17-dione, but also greatly enhanced the biocompatibility during the biotransformation process.

Uncinataflavone, a new flavonoid with a methyl benzoate substituent from Selaginella uncinata.

Uncinataflavone (1), a new flavonoid, together with four known compounds (2-5), was isolated from Selaginella uncinata (Desv.) Spring. Compounds 2 and 3 were isolated from the genus selaginella for the first time.

A new flavonoid with 6-phenyl substituent from Selaginella uncinata.

A new flavonoid, 6-(5-acetyl-2-methoxyphenyl)-apigenin (1), together with nine known compounds (2-10), was isolated from Selaginella uncinata (Desv.) Spring. This is the first report of the spectroscopic data of compound 3.

Polyflavanostilbene A, a new flavanol-fused stilbene glycoside from Polygonum cuspidatum.

Polyflavanostilbene A, a new flavanol-fused stilbene glycoside, was isolated from the rhizome of Polygonum cuspidatum. Its unusual structure, including its absolute stereochemistry, was determined by UV, IR, HRESIMS, and 1D and 2D NMR data and by the comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Polyflavanostilbene A has an unprecedented rearranged flavanol skeleton fused to stilbene via a hexahydrocyclopenta[c]furan moiety.

Selaginellin M, a new selaginellin derivative from Selaginella pulvinata.

A new selaginellin derivative, selaginellin M (1), together with one known compound, selaginellin E (2), was isolated from Selaginella pulvinata. The structure of the new compound was elucidated and named as (R,S)-4-((4'-hydroxy-4-((2-hydroxyethoxy)methyl))-3-((4-hydroxyphenyl)ethynyl)biphenyl-2-yl)(4-hydroxyphenyl)methylene)cyclohexa-2,5-dienone on the basis of the spectroscopic data including UV, IR, 1D, and 2D NMR as well as HR-ESI-MS analysis.

Two new selaginellin derivatives from Selaginella tamariscina (Beauv.) Spring.

Two new selaginellin derivatives, selaginellins K (1) and L (2), were isolated from Selaginella tamariscina (Beauv.) Spring and characterized as 2-formyl-4,4'-dihydroxy-3-[(4-hydroxyphenyl)ethynyl]biphene and 4,4'-dihydroxy-2-methyl-3-[(4-hydroxyphenyl)ethynyl]biphene on the basis of their spectroscopic data including UV, IR, 1D, and 2D NMR as well as HR-ESI-MS spectroscopic analysis.

A new flavonoid from Selaginella tamariscina (Beauv.) Spring.

A new flavonoid, 6-(2-hydroxy-5-carboxyphenyl)-apigenin (1), together with two new natural products, 3-(4-hydroxyphenyl)-6,7-dihydroxy coumarin (2), 1-methoxy-3-methylanthraquinone (3) and four known compounds, were isolated from Selaginella tamariscina (BEAUV.) SPRING. The structures of the new isolated compounds were elucidated on the basis of 1D and 2D NMR as well as ESI-HR-MS spectroscopic analysis.