Laurotetanine

Anonazepine, a new alkaloid from the leaves of Annona muricata (Annonaceae).[Pubmed:36544263]

Z Naturforsch C J Biosci. 2022 Dec 22;78(5-6):247-251.

From the CHCl(3)-soluble extract of Annona muricata L. (Annonaceae) leaves, one new 3-benzazepine-type alkaloid, anonazepine (1), and four known aporphine-type alkaloids, (+)-Laurotetanine (2), (+)-norglaucine (3), (-)-xylopine (4), and lanuginosine (5), were isolated. Except for (-)-xylopine (4), these remaining known alkaloids were first reported in A. muricata. The structures of the isolated alkaloids were established by 1D and 2D NMR spectroscopy and MS, as well as comparison with literature data. The new 3-benzazepine-type alkaloid existed in an inseparable mixture of two equilibrium conformers. Its absolute configuration was determined based on comparing their experimental and calculated ECD data. The anti-inflammatory activity of the isolated alkaloids was investigated, but none of the alkaloids showed a significant result.

Biochemical characterization of Peumus boldus fruits: Insights of its antioxidant properties through a theoretical approach.[Pubmed:34500293]

Food Chem. 2022 Feb 15;370:131012.

Peumus boldus is an endemic tree species from Chile whose leaves have been the focus of study for decades given that their infusions are reported to relieve rheumatic symptoms, headache, dyspepsia, urinary tract inflammation, and symptoms of other illnesses. These health properties have been studied mainly using leaves and bark, then it is relevant to know more about these properties in different parts of the plant. Considering the importance of P. boldus fruits in the diet of some rural populations, we analyzed their properties to explore its impact on the Chilean population health. Liquid chromatography and mass spectrometry analysis confirmed the presence of alkaloids such as boldine, although aporphine N-methyl-Laurotetanine was the most abundant. In addition, flavonoids catechin, chrysin and quercetin were also found in the extract. Cytotoxicity and anti-inflammatory activities of the fruit extract were invitro tested by using a murine macrophage cell model, observing that a diluted fraction of the extract was not cytotoxic, but showed anti-inflammatory activity, which is likely attributed to antioxidants activities. By means of quantum chemical calculations, we calculated the redox potential of the respective alkaloids and flavonoids found in the extract. Results suggest a synergistic effect between alkaloids and flavonoids, where boldine and N-methyl-Laurotetanine showed similar antioxidant properties. Finally, we present a description of the oxidation mechanisms for both groups of molecules which will sustain P. boldus fruit biological properties, in order to give this kind of fruits scientific value focusing on human health.

Two new isoquinoline alkaloids from the seeds of Nandina domestica.[Pubmed:31872787]

Nat Prod Res. 2021 Oct;35(19):3254-3260.

Two new isoquinoline alkaloids, 6 R,6aS-N-nantenine N(beta)-oxide (1), 6S,6aS-N-nantenine N(alpha)-oxide (2), along with nine known alkaloids, nantenine (3), oxonantenine (4), protopine (5), nornantenine (6), N-methyl-Laurotetanine (7), isocorydine (8), O-methyflavinantine (9), N-methyl-2,3,6-trimethoxymorphinan-dien-7-one N(beta)-oxide (10) and (+)-10-O-methylhernovine N(beta)-oxide (11) were isolated from the seeds of Nandina domestica. Their structures were elucidated by extensive analyses of spectroscopic data (IR, UV, HRESIMS, 1 D and 2 D NMR), ECD calculation and comparison with the related literatures. In addition, the cytotoxicity against A549 cells of these alkaloids was determined by the MTT assay.

Variation of the alkaloid content of Peumus boldus (boldo).[Pubmed:29454020]

Fitoterapia. 2018 Jun;127:179-185.

Eighteen alkaloids were detected in the bark, leaves, wood and roots of Peumus boldus, including traces of secoboldine, N-methylsecoboldine (boldine methine), glaucine and norreticuline, not reported previously as constituents of this species. Using appropriate standards, we quantified thirteen of them by UHPLC-MS/MS. Boldine was dominant in the bark, and laurolitsine in wood and roots. The alkaloid composition of the leaves, determined for 130 individually identified trees, classified by age and sex, was highly variable, where N-methylLaurotetanine, Laurotetanine, coclaurine and in some cases isocorydine predominated, but not boldine.

Computer-Aided (13)C NMR Chemical Profiling of Crude Natural Extracts without Fractionation.[Pubmed:28414230]

J Nat Prod. 2017 May 26;80(5):1387-1396.

A computer-aided, (13)C NMR-based dereplication method is presented for the chemical profiling of natural extracts without any fractionation. An algorithm was developed in order to compare the (13)C NMR chemical shifts obtained from a single routine spectrum with a set of predicted NMR data stored in a natural metabolite database. The algorithm evaluates the quality of the matching between experimental and predicted data by calculating a score function and returns the list of metabolites that are most likely to be present in the studied extract. The proof of principle of the method is demonstrated on a crude alkaloid extract obtained from the leaves of Peumus boldus, resulting in the identification of eight alkaloids, including isocorydine, rogersine, boldine, reticuline, coclaurine, Laurotetanine, N-methylcoclaurine, and norisocorydine, as well as three monoterpenes, namely, p-cymene, eucalyptol, and alpha-terpinene. The results were compared to those obtained with other methods, either involving a fractionation step before the chemical profiling process or using mass spectrometry detection in the infusion mode or coupled to gas chromatography.

Cholinesterase inhibitory activity of isoquinoline alkaloids from three Cryptocarya species (Lauraceae).[Pubmed:27492195]

Bioorg Med Chem. 2016 Sep 15;24(18):4464-4469.

Alzheimer's disease is the most common form of dementia among older adults. Acetylcholinesterase and butyrylcholinesterase are two enzymes involved in the breaking down of the neurotransmitter acetylcholine. Inhibitors for these enzymes have potential to prolong the availability of acetylcholine. Hence, the search for such inhibitors especially from natural products is needed in developing potential drugs for Alzheimer's disease. The present study investigates the cholinesterase inhibitory activity of compounds isolated from three Cryptocarya species towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Nine alkaloids were isolated; (+)-nornantenine 1, (-)-desmethylsecoantofine 2, (+)-oridine 3, (+)-Laurotetanine 4 from the leaves of Cryptocarya densiflora BI., atherosperminine 5, (+)-N-methylisococlaurine 6, (+)-N-methylLaurotetanine 7 from the bark of Cryptocarya infectoria Miq., 2-methoxyatherosperminine 8 and (+)-reticuline 9 from the bark of Cryptocarya griffithiana Wight. In general, most of the alkaloids showed higher inhibition towards BChE as compared to AChE. The phenanthrene type alkaloid; 2-methoxyatherosperminine 8, exhibited the most potent inhibition against BChE with IC50 value of 3.95muM. Analysis of the Lineweaver-Burk (LB) plot of BChE activity over a range of substrate concentration suggested that 2-methoxyatherosperminine 8 exhibited mixed-mode inhibition with an inhibition constant (Ki) of 6.72muM. Molecular docking studies revealed that 2-methoxyatherosperminine 8 docked well at the choline binding site and catalytic triad of hBChE (butyrylcholinesterase from Homo sapiens); hydrogen bonding with Tyr 128 and His 438 residues respectively.

[Chemical Constituents from the Roots of Lindera glauca and Their Antitumor Activity on Four Different Cancer Cell Lines].[Pubmed:30204386]

Zhong Yao Cai. 2016 Aug;39(8):1789-92.

OBJECTIVE: To study the chemical constitutes from the roots of Lindera glauca and the alkaloids influence on proliferation of HT-29,SGC-7901,SMMC-7721 and A549 cell lines. METHODS: The constituents were isolated by column chromatography such as RP-18,Sephadex LH-20 and silica gel,and their structures were elucidated by spectroscopic data analysis and compared with literature data. The antitumor activity was determined by MTT assay. RESULTS: Ten compounds had been isolated and identified as(-)-magnocurarine( 1),N-methyl-Laurotetanine( 2),Laurotetanine( 3),( +)-boldine( 4),(-)-norisoboldine( 5),( +)-norisocorydine( 6),pmethane-3,8-trans-diol( 7),p-methane-3,8-cis-diol( 8),eudesm-4( 15)-ene-7,11-diol( 9) and 4beta,6beta-dihydroxy-1alpha,5beta( H)-guai-9-ene( 10). Compounds 2 ~ 4 showed significant inhibitory activities against HT-29,SGC-7901,SMMC-7721 and A549 cells. CONCLUSION: Compound 1,9 and 10 are isolated from this plant for the first time. The IC50 value of compound 2 against HT-29 and SGC-7901 cell lines is even lower than VP-16.

Cytotoxic Alkaloids from the Stem of Xylopia laevigata.[Pubmed:27399666]

Molecules. 2016 Jul 8;21(7):890.

Xylopia laevigata (Annonaceae), known locally as "meiu" or "pindaiba", is widely used in folk medicine in Northeastern Brazil. In the present work, we performed phytochemical analyses of the stem of X. laevigata, which led to the isolation of 19 alkaloids: (-)-roemerine, (+)-anonaine, lanuginosine, (+)-glaucine, (+)-xylopine, oxoglaucine, (+)-norglaucine, asimilobine, (-)-xylopinine, (+)-norpurpureine, (+)-N-methylLaurotetanine, (+)-norpredicentrine, (+)-discretine, (+)-calycinine, (+)-Laurotetanine, (+)-reticuline, (-)-corytenchine, (+)-discretamine and (+)-flavinantine. The in vitro cytotoxic activity toward the tumor cell lines B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), K562 (human chronic myelocytic leukemia) and HL-60 (human promyelocytic leukemia) and non-tumor peripheral blood mononuclear cells (PBMCs) was tested using the Alamar Blue assay. Lanuginosine, (+)-xylopine and (+)-norglaucine had the highest cytotoxic activity. Additionally, the pro-apoptotic effects of lanuginosine and (+)-xylopine were investigated in HepG2 cells using light and fluorescence microscopies and flow cytometry-based assays. Cell morphology consistent with apoptosis and a marked phosphatidylserine externalization were observed in lanuginosine- and (+)-xylopine-treated cells, suggesting induction of apoptotic cell death. In addition, (+)-xylopine treatment caused G(2)/M cell cycle arrest in HepG2 cells. These data suggest that X. laevigata is a potential source for cytotoxic alkaloids.

In vitro antiplasmodial and antioxidant activities of bisbenzylisoquinoline alkaloids from Alseodaphne corneri Kosterm.[Pubmed:27086149]

Asian Pac J Trop Med. 2016 Apr;9(4):328-332.

OBJECTIVE: To study antiplasmodial and antioxidant activities of the isolation of alkaloids from the active dichloromethane extract of Alseodaphne corneri. METHODS: Phytochemical studies of the crude extract led to the isolation of six alkaloids using recycle high performance liquid chromatography and preparative thin layer chromatography. The antiplasmodial activity of the isolated compounds was evaluated using the histidine-rich protein II assay. The isolated alkaloids were also tested for their antioxidant activity using three different assays; DPPH, ferric reducing ability of plasma and metal chelating assays. RESULTS: Malaria infection caused the formation of free radicals which subsequently led to oxidative stress and apoptosis. The antioxidant properties of the alkaloids under investigation revealed that in addition to the antiplasmodial activity, the alkaloids could also prevent oxidative stress. (+)-Laurotetanine and (+)-norstephasubine exhibited strong antiplasmodial activities with IC50 values of 0.189 and 0.116 muM, respectively. CONCLUSIONS: Interestingly, the two most potent compounds that exhibit antiplasmodial activity also exhibit good antioxidant activities. The crude dichloromethane extract and the isolated compounds exert substantial antiplasmodial and antioxidative activities which in turn suppress oxidative stress and cause less damage to the host.

Anti-malarial Activity of Isoquinoline Alkaloids from the Stem Bark of Actinodaphne macrophylla.[Pubmed:26594753]

Nat Prod Commun. 2015 Sep;10(9):1541-2.

Seven isoquinoline alkaloids isolated from the bark of Actinodaphne macrophylla in this study demonstrated in vitro antiplasmodial activities against Plasmodium falciparum 3D7 with IC50 values of 0.08 microM, 0.05 microM, 1.18 microM, 3.11 microM, 0.65 microM, 0.26 microM, and 1.38 microM for cycleanine, 10-demethylxylopinine, reticuline, Laurotetanine, bicuculine, alpha-hydrastine and anolobine, respectively, which are comparable with the reference standard, chloroquine. 10-Demethylxylopinine was found to be the most active of these compounds.

[Aporphine alkaloids from Litsea greenmaniana].[Pubmed:25993795]

Zhongguo Zhong Yao Za Zhi. 2015 Jan;40(1):94-7.

A new aporphine alkaloid (1), together with five known analogues (2-6), has been isolated from the branch of Litsea greenmaniana by using various chromatographic techniques. Their structures were identified by spectroscopic data analysis ( MS, IR, 1D and 2D NMR) as 2,9-dihydroxy-1,10-dimethoxy-4,5-dihydro-7-oxoaporphine (1), Laurotetanine (2), N-methylLaurotetanine (3), isodomesticine (4), isocorydine (5), and norisocorydine (6). Compound 1 was a new compound, and compounds 2-6 were obtained from this plant for the first time.

[Alkaloids from roots and stems of Litsea cubeba].[Pubmed:25751947]

Zhongguo Zhong Yao Za Zhi. 2014 Oct;39(20):3964-8.

A phytochemical investigation on the roots and stems of Litsea cubeba led to the isolation of seven isoquinolone alkaloids. By spectroscopic analysis and comparison of their 1H and 13C-NMR data with those in literatures, these alkaloids were identified as (+)-norboldine (1), (+)-boldine (2), (+)-reticuline (3), (+)-Laurotetanine (4), (+)-isoboldine (5), (+)-N-methyl-Laurotetanine (6), and berberine (7), respectively. Among them, 7 was isolated from the genus for the first time. The evaluation of these compounds showed weak anti-inflammatory activity against NO production in RAW 267.4 and BV-2 cells.

Memory enhancement by traditional Chinese medicine?[Pubmed:23249175]

J Biomol Struct Dyn. 2013 Dec;31(12):1411-39.

Cognitive repair by insulin-like growth factor-I (IGF-I) through activation of insulin-like growth factor-I receptor (IGF-IR) is well established, but not used for clinical therapy due to its link to cancer. We hypothesize that IGF-IR activation rather than IGF-I per se may be essential for cognitive repair and attempted to identify ligands from traditional Chinese medicine (TCM) with drug-like potential towards IGF-IR. TCM ligands, 3-(2-carboxyphenyl)-4(3H)-quinazolinone from Isatisin digotica, (+)-N-methylLaurotetanine from Lindera aggregate, and (+)-1(R)-Coclaurine from Nelumbonucifera Gaertn, exhibited high binding affinities and good blood brain barrier (BBB) penetration crucial for accessing IGF-IR. Stable complex formation of the candidates was observed during molecular dynamics (MD) simulation. Interactions with Leu975 and Gly1055 or Asp1056 were important for ligand binding. Amino acid distance analysis revealed residues 974/975, 984-986, 996-1006, 1040-1056, and 1122-1135 as "hotspots" for ligand binding in IGF-IR. Versatile entry pathways for the TCM candidates suggest high accessibility to the binding site. Blockage of the binding site opening by the TCM candidates limits binding site access by other compounds. Multiple linear regression (R(2) = 0.9715), support vector machine (R(2) = 0.9084), Bayesian network (R(2) =0.8233) comparative molecular field analysis (CoMFA, R(2) = 0.9941), and comparative molecular similarity indices analysis (CoMSIA, R(2) = 0.9877) models consistently suggest that the TCM candidates might exert bioactivity on IGF-IR. Contour of representative MD conformations to CoMFA and CoMSIA maps exhibits similar results. Properties including BBB passage, evidence of ability to form stable complexes with IGF-IR by MD simulation, and predicted bioactivity suggest that the TCM candidates have drug-like properties and might have potential as cognitive-enhancing drugs.