Unusual Lactone Research Articles

Triterpenoid and Coumarin Isolated from Astilbe grandis with Anti-Inflammatory Effects through Inhibiting the NF-κB Pathway in LPS-Induced RAW264.7 Cells.

The roots of Astilbe grandis, known as "Ma sang gou bang", are used as a Miao traditional medicine with anti-inflammatory and analgesic properties. However, the active components and mechanism of action of this plant remain mostly uncharacterized. The aim of this study was to identify its active components and verify their pharmacological activity. The extract of A. grandis root was separated using various chromatographic methods. As a result, we obtained one novel triterpenoid, named astigranlactone (1), which has an unusual lactone moiety formed between C-7 and C-27. Additionally, a known coumarin compound, 11-O-galloyl bergenin (2) was isolated from this plant. The structures of these two compounds were elucidated by extensive NMR experiments in conjunction with HR-ESI-MS data. To the best of our knowledge, both compounds were isolated from this species for the first time. Moreover, we tested the anti-inflammation effect of the two compounds by establishing a cellular inflammation model induced by LPS in RAW264.7 cells. The effect of different concentrations of these compounds on the activity of RAW264.7 cells was assessed using a CCK8 assay. The levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in the supernatant of each group were evaluated using the Griess method and an enzyme-linked immunosorbent assay (ELISA). Western blot and quantitative real-time PCR (qRT-RCR) were used to measure the levels of cyclooxygenase 2 (COX-2) and nitric oxide synthase (iNOS) gene expression. Our findings revealed that these two compounds inhibited the high levels of NO, TNF-α, IL-6, IL-1β, COX-2, and iNOS (induced by LPS). Mechanistic studies demonstrated that these two compounds reduced the activation of the nuclear transcription factor-B (NF-κB) signaling pathway by inhibiting the phosphorylation of p65. Therefore, our study indicates that compounds 1 and 2 can exert a definite anti-inflammatory effect by inhibiting the NF-κB signaling pathway.

3,4-Seco-Isopimarane Diterpenes from the Twigs and Leaves of Isodon Flavidus.

Three isopimarane diterpenes [fladins B (1), C (2), and D (3)] were isolated from the twigs and leaves of Chinese folk medicine, Isodon flavidus. The chemical structures were determined by the analysis of the comprehensive spectroscopic data, and the absolute configuration was confirmed by X-ray crystallographic analysis. The structures of 1–3 were formed from isopimaranes through the rearrangement of ring A by the bond break at C-3 and C-4 to form a new δ-lactone ring system between C-3 and C-9. This structure type represents the first discovery of a natural isopimarane diterpene with an unusual lactone moiety at C-9 and C-10. In the crystal of 1, molecules are linked to each other by intermolecular O-H···O bonds, forming chains along the b axis. Compounds 1–3 were evaluated for their bioactivities against different diseases. None of these compounds displayed cytotoxic activities against HCT116 and A549 cancer cell lines, antifungal activities against Trichophyton rubrum and T. mentagrophytes, or antiviral activities against HIV entry at 20 µg/mL (62.9–66.7) µM. Compounds 1 and 3 did not show antiviral activities against Ebola entry at 20 µg/mL either; only 2 was found to show an 81% inhibitory effect against Ebola entry activity at 20 µg/mL (66.7 µM). The bioactivity evidence suggested that this type of compound could be a valuable antiviral lead for further structure modification to improve the antiviral potential.

Bioactive Compounds from Euphorbia usambarica Pax. with HIV-1 Latency Reversal Activity

Euphorbia usambarica is a traditional medicine used for gynecologic, endocrine, and urogenital illnesses in East Africa; however, its constituents and bioactivities have not been investigated. A variety of compounds isolated from Euphorbia species have been shown to have activity against latent HIV-1, the major source of HIV-1 persistence despite antiretroviral therapy. We performed bioactivity-guided isolation to identify 15 new diterpenoids (1–9, 14–17, 19, and 20) along with 16 known compounds from E. usambarica with HIV-1 latency reversal activity. Euphordraculoate C (1) exhibits a rare 6/6/3-fused ring system with a 2-methyl-2-cyclopentenone moiety. Usambariphanes A (2) and B (3) display an unusual lactone ring constructed between C-17 and C-2 in the jatrophane structure. 4β-Crotignoid K (14) revealed a 250-fold improvement in latency reversal activity compared to crotignoid K (13), identifying that configuration at the C-4 of tigliane diterpenoids is critical to HIV-1 latency reversal activity. The primary mechanism of the active diterpenoids 12–14 and 21 for the HIV-1 latency reversal activity was activation of PKC, while lignans 26 and 27 that did not increase CD69 expression, suggesting a non-PKC mechanism. Accordingly, natural constituents from E. usambarica have the potential to contribute to the development of HIV-1 eradication strategies.

Allocyclinones, hyperchlorinated angucyclinones from Actinoallomurus.

A screening program on a limited number of strains belonging to the Actinoallomurus genus yielded a series of new angucyclinones. NMR and MS analyses established that these compounds are characterized by an unusual lactone ring and present up to four halogens per molecule, with one congener representing the first natural product containing a trichloromethyl substitution on an aromatic system. Remarkably, this family of metabolites seems to be produced by phylogenetically distinct Actinoallomurus isolates. Because of the unique structural features and wide distribution among Actinoallomurus, we have designated these angucyclinones as allocyclinones. Allocyclinones possess interesting activity against different Gram-positive bacteria, including antibiotic-resistant strains, with antibacterial potency increasing with the number of chlorine substituents. The tetrachlorinated compound is the most abundant congener in the allocyclinone complex.

Unusual microbial lactonization and hydroxylation of asiatic acid by Umbelopsis isabellina

Asiatic acid (1) is a natural triterpenoid isolated from Centella asiatica. This paper reports the microbial transformation of asiatic acid by an endophytic fungus Umbelopsis isabellina to obtain derivatives potentially useful for further studies. Incubation of asiatic acid with U. isabellina afforded two derivatives 2α,3β,7β, 23-tetrahydroxyurs-12-ene-28-oic acid (2) and 2α,3β,7β,23-tetrahydroxyurs-11-ene-28,13-lactone (3). The structures of these compounds were elucidated by spectral data. Compound 3 has formed an unusual lactone. These two products are new compounds. The possible transformation passway was also discussed.

Baeckeins A and B, Two Novel 6‐Methylflavonoids from the Roots of Baeckea frutescens

AbstractA pair of novel isomeric 6‐methylflavonoids, named baeckeins A (1) and B (2), were isolated from the roots of Baeckea frutescens. The two compounds possess a unique C23 skeleton, resulting from the 6‐methylation and 8‐arylation of a flavonol (=3‐hydroxy‐2‐phenyl‐4H‐1‐benzopyran‐4‐one) framework and the formation of an unusual lactone ring E. Their structures were elucidated by detailed spectroscopic analyses, including HR‐ESI‐MS and 1D‐ and 2D‐NMR data (HSQC, HMBC, and ROESY). A plausible biogenetic pathway for compounds 1 and 2 is also proposed (Scheme).

ChemInform Abstract: Swerilactones E‐G, Three Unusual Lactones from Swertia mileensis.

AbstractSignificant anti‐HBV activity in vitro is observed for swerilactone E (I) and F (II).

Swerilactones E–G, three unusual lactones from Swertia mileensis

Swerilactones E (1), F (2), and G (3), three unusual lactones with a phenyl group, were isolated from the traditional Chinese herb of Sweat mileensis. Their structures were determined based on extensive spectroscopic analysis and X-ray single crystal crystallography. Our anti-HBV assay on the Hep G 2.2.15 cell line in vitro showed that compounds 1 and 2 exhibited significant inhibitory activities against the secretion of HBsAg with IC(50) of 0.22 and 0.70 mM and HBeAg with IC(50) of 0.52 and >6.78 nM, respectively. (C) 2010 Elsevier Ltd. All rights reserved.

GilR, an Unusual Lactone‐Forming Enzyme Involved in Gilvocarcin Biosynthesis

Last at last: The terminal step of the gilvocarcin V (GV) biosynthetic pathway is an unusual lactone formation. Here we show that the enzyme, GilR, dehydrogenates the hemiacetal moiety of pregilvocarcin V to the lactone found in GV by using covalently bound FAD.

Antiviral Activity of Natural and Synthetic Brassinosteroids

Since the discovery of brassinolide, a C28 steroid with an unusual lactone B-ring structure, more than 60 related compounds -collectively known as brassinosteroids (BRs) - have been isolated from a wide variety of plant species. Exogenous application of BRs to plants at nanomolar to micromolar concentrations has a broad spectrum of growth responses, such as stem elongation, inhibition of root growth, promotion of cell division and enhancement of stress resistance, brought about by changes in enzyme activity and gene expression. In the last years, biochemical and genetic analysis provided compelling evidence for an essential role of BRs in plant development. In this paper, we review our synthetic methods to obtain BRs analogues and report the scope of antiviral activity of these compounds against RNA and DNA viruses. Some of the compounds showed selectivity indexes (SI) 10- to 18- fold higher than ribavirin, a broad spectrum antiviral compound, when tested against Junin virus (JV) (Arenaviridae); a good antiviral activity against measles virus (MV) (Paramixoviridae), with SI values also higher than ribavirin used as reference drug, and a similar or lower activity against herpes simplex type 1 and 2 (HSV-1 and HSV-2) (Herpesviridae) when compared to foscarnet or acyclovir, respectively. Structure activity relationship studies (SAR) are analyzed, in order to detect which stereochemistry, type and position of functional groups are needed to develop a selective class of virus inhibitors. Keywords: antiviral, brassinosteroids derivatives, measles virus, herpes simplex virus, arenaviridae

Iron(III)chloride oxidation of tricarbonyl(vinylketene)iron(0)-alkyne adducts

Oxidation of the adducts formed from tricarbonyl(vinylketene)iron(0) complexes and alkynes by iron(III) chloride in methanol/water leads to the replacement of the tricarbonyliron(0) unit with an oxygen atom derived from the water. This pathway to furan-3(2H)-ones requires the presence of an electron-withdrawing substituent on carbon-2 of the vinylketene–alkyne adduct. Data used to assign the structures of some of the vinylketene–alkyne adducts used in this study included an X-ray crystal structure analysis of the unusual lactone complex 5c.

Stryspinolactone, an unusual monoterpene lactone from Strychnos spinosa

The structure of stryspinolactone, an unusual lactone from Strychnos spinosa, was determined from spectroscopic data.