Labdane Research Articles

Cytotoxic labdane-type diterpenes from Hedychium longipetalum inhibiting production of nitric oxide.

Three new labdane diterpenes, hedylongnoids A (1), B (2) and C (3), were isolated from the rhizomes of Hedychium longipetalum, together with three known ones yunnancoronarin A (4), hedyforrestin C (5) and hedyforrestin B (6). Their structures were established by spectroscopic analysis, including 2D-NMR spectroscopic techniques. Compounds 1-6 exhibited inhibitory effects against nitric oxide (NO) production in LPS and IFN-γ-induced RAW 264.7 murine macrophages with IC50 values ranging from 0.56 to 7.50 μg/ml, and 3-6 showed cytotoxicities against cancer cell lines SGC-7901 and Hela with IC50 values ranging from 6.21 to 14.53 μg/ml and from 6.58 to 14.83 μg/ml, respectively.

New Labdane Diterpenes and Their Glycoside Derivatives from the Roots of Isodon adenantha

Two new labdane-type diterpenes (adenanthic acids A and B; 1 and 2, resp.) and three new labdane diterpene glycosides (adenanthosides A-C; 3-5, resp.) were isolated from the roots of Isodon adenantha, together with 23 known constituents including seven diterpenoids (6-12), eight triterpenoids (13-20), one lignan glycoside (21), six steroids (22-27), and one ceramide (28). Their structures were elucidated by spectroscopic methods including extensive 2D-NMR techniques. Cytotoxicity and antibacterial activities of the samples were measured by the MTT method and the filter paper disc agar diffusion method. But none of them showed significant activities.

SPECTROSCOPIC DATA OF LABDANE DITERPENES: A THEORETICAL ANALYSIS VIA NMR AND DFT

Labdane diterpenes exhibit important bioactivities such as cardiovascular effects in rats as well as effects in the treatment of autoimmune diseases and Alzheimer syndrome. Recently, the labdane diterpenes ent-13-epi-manoil oxide, ribenone and ribenol were isolated from Croton palanostigma. The computational method DFT/B3LYP/cc-pVDZ was used to optimize the structures of these diterpenes and to calculate infrared data. Chemical shifts (δH and δC) of the minimum energy structures (local minimum) were calculated and compared with the experimental data. Comparison of the NMR data by simple linear regression (SLR) showed satisfactory statistical results with a correlation coefficient (R2) and predictive ability (Q2) of over 98%. The predicted NMR data were used to confirm the δH values that have not been published.

ChemInform Abstract: Synthesis of Labdane Diterpenes Galanal A (I) and B (II) from (+)‐Sclareolide.

ChemInform Abstract: Synthesis of Labdane Diterpenes Galanal A (I) and B (II) from (+)‐Sclareolide.

Molecular docking and inhibition kinetics of α-glucosidase activity by labdane diterpenes isolated from tora seeds (Alpinia nigra B.L. Burtt.).

Current approach against type 2 diabetes involves α-glucosidase inhibitors like acarbose associated with many side effects. Therefore, as an alternative to the existing drug, many natural products mainly from plant sources have been investigated which inhibit α-glucosidase. Here, we have selected medicinally important Alpinia nigra to explore its α-glucosidase inhibitory activity. Organic extracts of seeds and two purified natural diterpenes I: (E)-labda-8(17), 12-diene-15, 16-dial and II: (E)-8β, 17-epoxylabd-12-ene-15, 16-dial from A. nigra were investigated towards inhibition of α-glucosidase activity. Dose-dependent inhibition pattern were observed for seed extracts and both the compounds. Further, inhibition kinetics studies of the diterpenes indicated a non-competitive type of inhibition against α-glucosidase. Docking studies were carried out which revealed that both the diterpenes interacted within the active site of N-terminal and C-terminal domain of human maltase-glucoamylase enzyme, respectively. This is the first report of α-glucosidase inhibitory activity of these isolated diterpenes and their higher inhibitory potential than any terpenoids studied till date against α-glucosidase.

In vitro bactericidal activity of diterpenoids isolated from Aframomum melegueta K. Schum against strains of Escherichia coli, Listeria monocytogenes and Staphylococcus aureus

Abstract Ethnopharmacological relevance The ethnobotanical use of Aframomum melegueta in the treatment of urinary tract and soft tissue infection suggested that the plant has antimicrobial activity. Materials and methods To substantiate the folkloric claims, an acetone, 50:50 acetone:methanol and 2:1 chloroform:methanol extracts were tested against Escherichia coli K12 ; acetone extract and the fractions of acetone extracts were tested against Listeria monocytogenes . Bioassay-guided fractionation was performed on the extract using L. monocytogenes as the test organism to isolate the bioactive compounds which were then tested against all the other organisms. Results Four known labdane diterpenes (G3 and G5) were isolated for the first time from the rhizomes of A. melegueta and purified. These were tested against E. coli , L. monocytogenes , methicillin resistant Staphylococus aureus (MRSA) and S. aureus to determine antibacterial activity. The result showed that two compounds G3 and G5 exhibited more potent antibacterial activity compared to the current clinically used antibiotics ampicillin, gentamicin and vancomycin and can be potential antibacterial lead compounds. The structure of the labdane diterpenes were elucidated using nuclear magnetic resonance (NMR) spectroscopy and Mass spectrometry. A possible mode of action of the isolated compound G3 and its potential cytotoxicity towards mammalian cells were also discussed. Conclusion The results confirmed the presence of antibacterial compounds in the rhizomes of A. melegueta with a favourable toxicity profile which could be further optimized as antibacterial lead compounds.

Unveiling the effect of plant derived labdane diterpenes as promising bactericidal and anticancer agents

Unveiling the effect of plant derived labdane diterpenes as promising bactericidal and anticancer agents

Cancer chemoprevention activity of labdane diterpenes from rhizomes of Hedychium coronarium

Hedychium coronarium J. Koenig, Zingiberaceae, is a medicinal plant popularly used to treat inflammatory conditions in different countries. Three labdane diterpenes [isocoronarin D (1), methoxycoronarin D (2), ethoxycoronarin D (3)] and benzoyl eugenol (4) were isolated from rhizomes and their chemopreventive potential was evaluated using in vitro assays, namely the inhibition of NF-κB, COX-1 and -2, the induction of antioxidant response element (ARE), and the inhibition of cell proliferation. Diterpene 1 activated ARE (EC50 57.6 ± 2.4μM), while 2, 3 and 4 significantly inhibited NF-κB (IC50 of 7.3 ± 0.3, 3.2 ± 0.3 and 32.5 ± 4.9μM, respectively). In addition, 2 and 3 selectively inhibited COX-1 (IC50 values of 0.9 ± 0.0 and 3.8 ± 0.0μM, respectively). These data support the potential chemopreventive activity of constituents from H. coronarium rhizomes.

Molecular docking and inhibition studies of α-amylase activity by labdane diterpenes from Alpinia nigra seeds

Wide varieties of synthetic drugs are available for combating type 2 diabetes but are not free of associated side effects. Commercially available antidiabetic drugs are known to be potent inhibitors of α-amylase which reduce postprandial hyperglycaemia. Here, we have investigated Alpinia nigra seed extracts and the isolated two labdane diterpenes (I and II) for the α-amylase inhibitory activity. These labdane type diterpenes showed more promising inhibitory effects (IC50 value 24.3 ± 2.05 and 15.167 ± 0.52 μM for compound I and II, respectively) against α-amylase than the standard inhibitor, acarbose. For both compounds, the mode of enzymatic inhibition was found to be non-competitive with K i 13.303 ± 0.065 and 12.19 ± 0.099 μM, respectively. Molecular docking studies revealed that both I and II bind the human pancreatic α-amylase in the active site cleft similar to the acarbose. Among all the compounds under investigation, acarbose and compound II were found to have the highest MolDock and re-rank score. Further molecular dynamic simulation studies also supports the docking results obtained for both I and II. This is the first report on α-amylase inhibitory effect of the two labdane diterpenes with their potential candidature as future antidiabetic drugs of herbal origin.

Synthesis of labdane diterpenes galanal A and B from (+)-sclareolide.

The first chemical synthesis of galanal A and B was achieved by a concise and highly efficient pathway starting from commercially available (+)-sclareolide and features a Wittig reaction and a titanocene-mediated radical cyclization as the key steps.

Isolation and characterization of six labdane diterpenes and one pregnane steroid of Turraeanthus africanus

Six labdane diterpene derivatives, named turraeanins F–J (3–6, 8) and epi-turraeanin J (7), and a pregnane steroid derivative named turraeasterodionene (2), were isolated by preparative high performance liquid chromatography together with thirteen known compounds from the Cameroonian medicinal plant Turraeanthus africanus. Their structures were elucidated by means of nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry in conjunction with the published data for the analogs, as well as the fragmentation patterns of each compound. Most of the known compounds were obtained for the first time from this plant. The compounds (2–7) were tested for their antibacterial efficacies against both Gram-positive and Gram-negative bacteria, including some clinically-important Risk group 2 human pathogens. Compound 4 exhibited the most pronounced antibacterial effectiveness comparable to standard reference streptomycin, with more potency against Gram-positive than Gram-negative bacteria. By comparing compounds 3, 4 and 5, a tentative structure–activity relationship could be drawn; selected oxidations at C-16 and C-18 drastically reduced the antibacterial efficacy of the parent compound (4). These results revealed the potential of compound 4 as a suitable antibacterial lead compound that might be used for further development of other derivatives to increase the antimicrobial efficacy.

In vitro bactericidal activity of diterpenoids isolated from Aframomum melegueta K.Schum against strains of Escherichia coli, Listeria monocytogenes and Staphylococcus aureus

Ethnopharmacological relevanceThe ethnobotanical use of Aframomum melegueta in the treatment of urinary tract and soft tissue infection suggested that the plant has antimicrobial activity. Materials and methodsTo substantiate the folkloric claims, an acetone, 50:50 acetone:methanol and 2:1 chloroform:methanol extracts were tested against Escherichia coli K12; acetone extract and the fractions of acetone extracts were tested against Listeria monocytogenes. Bioassay-guided fractionation was performed on the extract using L. monocytogenes as the test organism to isolate the bioactive compounds which were then tested against all the other organisms. ResultsFour known labdane diterpenes (G3 and G5) were isolated for the first time from the rhizomes of A. melegueta and purified. These were tested against E. coli, L. monocytogenes, methicillin resistant Staphylococus aureus (MRSA) and S. aureus to determine antibacterial activity. The result showed that two compounds G3 and G5 exhibited more potent antibacterial activity compared to the current clinically used antibiotics ampicillin, gentamicin and vancomycin and can be potential antibacterial lead compounds. The structure of the labdane diterpenes were elucidated using nuclear magnetic resonance (NMR) spectroscopy and Mass spectrometry. A possible mode of action of the isolated compound G3 and its potential cytotoxicity towards mammalian cells were also discussed. ConclusionThe results confirmed the presence of antibacterial compounds in the rhizomes of A. melegueta with a favourable toxicity profile which could be further optimized as antibacterial lead compounds.

ChemInform Abstract: Unveiling the Mode of Action of Antibacterial Labdane Diterpenes from Alpinia nigra (Gaertn.) B. L. Burtt Seeds.

AbstractThe labdane triterpenes (I) and (II) show significant activity for damaging and disintegrating cell membranes of several Gram‐positive, as well as Gram‐negative bacteria cell lines.

Antimicrobial activity and chemical analysis of Microlicia hatschbachii Wurdack (Melastomataceae) extract

Aerial parts of Microlicia hatschbachii were extracted with hexane, and the extract was evaluated for antimicrobial activity by a broth dilution method. After phytochemical procedures: GC-MS identified aliphatic alkanes, carboxylic acids and methyl esters of long-chain fatty acids; and two diterpenoids [labd-8(17)-en-15-oic acid and labd-8(17),13-dien-15-oic acid] were identified by 1H and 13C NMR. The antimicrobial activity of the hexane extract could be attributed to the presence of labdanes. This identification is the first reported occurrence of labdane diterpenes in the Melastomataceae family.

ChemInform Abstract: Two New Labdane Diterpenes from Fresh Leaves of Leonurus japonicus and Their Degradation During Drying.

ChemInformVolume 44, Issue 42 Natural Products ChemInform Abstract: Two New Labdane Diterpenes from Fresh Leaves of Leonurus japonicus and Their Degradation During Drying. Hiroyuki Fuchino, Res. Cent. Med. Plant Resour., Natl. Inst. Biomed. Innovation, Tsukuba, Ibaraki 305, JapanSearch for more papers by this authorAkihiro Daikonya, Res. Cent. Med. Plant Resour., Natl. Inst. Biomed. Innovation, Tsukuba, Ibaraki 305, JapanSearch for more papers by this authorTakeo Kumagai, Res. Cent. Med. Plant Resour., Natl. Inst. Biomed. Innovation, Tsukuba, Ibaraki 305, JapanSearch for more papers by this authorYukihiro Goda, Res. Cent. Med. Plant Resour., Natl. Inst. Biomed. Innovation, Tsukuba, Ibaraki 305, JapanSearch for more papers by this authorYutaka Takahashi, Res. Cent. Med. Plant Resour., Natl. Inst. Biomed. Innovation, Tsukuba, Ibaraki 305, JapanSearch for more papers by this authorNobuo Kawahara, Res. Cent. Med. Plant Resour., Natl. Inst. Biomed. Innovation, Tsukuba, Ibaraki 305, JapanSearch for more papers by this author Hiroyuki Fuchino, Res. Cent. Med. Plant Resour., Natl. Inst. Biomed. Innovation, Tsukuba, Ibaraki 305, JapanSearch for more papers by this authorAkihiro Daikonya, Res. Cent. Med. Plant Resour., Natl. Inst. Biomed. Innovation, Tsukuba, Ibaraki 305, JapanSearch for more papers by this authorTakeo Kumagai, Res. Cent. Med. Plant Resour., Natl. Inst. Biomed. Innovation, Tsukuba, Ibaraki 305, JapanSearch for more papers by this authorYukihiro Goda, Res. Cent. Med. Plant Resour., Natl. Inst. Biomed. Innovation, Tsukuba, Ibaraki 305, JapanSearch for more papers by this authorYutaka Takahashi, Res. Cent. Med. Plant Resour., Natl. Inst. Biomed. Innovation, Tsukuba, Ibaraki 305, JapanSearch for more papers by this authorNobuo Kawahara, Res. Cent. Med. Plant Resour., Natl. Inst. Biomed. Innovation, Tsukuba, Ibaraki 305, JapanSearch for more papers by this author First published: 01 October 2013 https://doi.org/10.1002/chin.201342198Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume44, Issue42October 15, 2013 RelatedInformation

Phytochemical profiling of Curcuma kwangsiensis rhizome extract, and identification of labdane diterpenoids as positive GABAA receptor modulators

An ethyl acetate extract of Curcuma kwangsiensis S.G. Lee & C.F. Liang (Zingiberaceae) rhizomes (100 μg/ml) enhanced the GABA-induced chloride current (IGABA) through GABAA receptors of the α1β2γ2S subtype by 79.0±7.0%. Potentiation of IGABA was measured using the two-microelectrode voltage-clamp technique and Xenopus laevis oocytes. HPLC-based activity profiling of the crude extract led to the identification of 11 structurally related labdane diterpenoids, including four new compounds. Structure elucidation was achieved by comprehensive analysis of on-line (LC-PDA-ESI-TOF-MS) and off-line (microprobe 1D and 2D NMR) spectroscopic data. The absolute configuration of the compounds was established by comparison of experimental and calculated ECD spectra. Labdane diterpenes represent a new class of plant secondary metabolites eliciting positive GABAA receptor modulation. The highest efficiency was observed for zerumin A (maximum potentiation of IGABA by 309.4±35.6%, and EC50 of 24.9±8.8 μM).

Labdane diterpenes from Chloranthus serratus

Five new labdane diterpenes (1–5), serralabdanes A–E, were isolated from the whole plant of Chloranthus serratus. Their structures were elucidated by spectroscopic methods, and the absolute configuration of the 12,13-diol moiety in serralabdane C (3) was determined by observing the induced circular dichroism (ICD) after addition of dimolybdenum teracetate in DMSO solution. Serralabdanes A–E (1–5) showed inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells.

Determination of configuration at C-13 of (-)-ent-8β-hydroxy-labdan-15-oic acid and its biotransformation by Battus polydamas larvae

Battus polydamas (Linnaeus, 1758) is a specialist phytophagous insect and its larva feed on Aristolochiaceae species, of which were isolated, among other compounds, nitro derivatives, lignoids, and diterpenoids [1]. Species belonging to the Aristolochia genus contain insecticidal or deterrent compounds to the majority of insects, supporting the hypothesis that such compounds represent barriers to colonization by other non-adapted lepidopteran larvae [2]. Biotransformation studies by B. polydamas and other Aristolochiaceae-feeder have focused mainly on aristolochic acids, which have a 3,4-methylenedioxy-10-nitrophenanthrenic-1-acid carbon skeleton. In this study, B. polydamas larvae were fed at laboratory with leaves of Aristolochia giberti, and methanolic extracts of the leaves and feces were prepared by maceration. The chemical profiles of these extracts were compared by HPLC-PDA, NMR, LC-MS, and TLC. From both extracts a new labdane diterpene, (–)-ent-8β-hydroxy-labdan-15-oic acid (1), was isolated. The configuration at C-13 of 1 was established as R by the PGME method [3], whereas the absolute configuration of trans-decalin system was proposed on basis NMR spectroscopic data and in the negative signal of the optical activity observed. In addition, two new labdane diterpenes, (–)-ent-8β,18α-dihydroxy-labdan-15-oic acid (2) and (–)-ent-8β-hydroxy-labdan-15,18-dioic acid (3), possibly sequential oxidation products of 1, were isolated from feces extract and their structures were determined by spectroscopic analyses. The biotransformation of 1 into 2 and 3 and the excretion of these compounds in the feces suggest that 1 is detoxified by B. polydamas. The larvae also stored compound 3, but its ecological role is still unclear.

Unveiling the mode of action of antibacterial labdane diterpenes from Alpinia nigra (Gaertn.) B. L. Burtt seeds

The labdane diterpene, (E)-labda-8(17), 12-diene-15, 16-dial (compound A) and its epoxide analogue, (E)-8β, 17-Epoxylabd-12-ene-15, 16-dial (compound B) were isolated from the seeds of Alpinia nigra for the first time. The antibacterial activities of both compounds were evaluated against three Gram-positive and four Gram-negative bacteria, and flow cytometric analysis revealed that these compounds caused significant damage to the bacterial cell membranes. Further, field emission scanning electron microscope imaging and cell leakage analysis confirmed that the labdane diterpenes were responsible for bacterial cell membrane damage and disintegration. Our findings provide new insight into the broad-spectrum effects of two natural labdane diterpenes that may be useful in the future development of herbal antibiotic products.

Tetracyclic Diterpenoids with Isomerized Isospongian Skeleton and Labdane Diterpenoids from the Fruits of Amomum kravanh

Four novel diterpenoids, including three tetracyclic diterpenes with isomerized isospongian skeletons, kravanhins A-C (1-3), and kravanhin D (4), and three new labdane diterpenes (5-7) were isolated from the fruits of Amomum kravanh. Compounds 1-4 had unprecedented isospongian diterpene skeletons with a trans-anti-cis fused tricyclic ring system. The structures of compounds 1-7 were established on the basis of extensive analysis of NMR spectra, CD, and X-ray crystallography. Compound 2 showed inhibitory activity on nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophages with an IC(50) value of 36.2 μM.