The Structure of Tubulosine, a Novel Alkaloid from <i>Pogonopus tubulosus</i> (DC.) Schumann

Brauchli, P.; Deulofeu, Venancio; Budzikiewicz, H.; Djerassi, Carl

doi:10.1021/ja01063a079

Cited by 30 publications

(13 citation statements)

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“…Hydroxylation at C-6' of (3, to give didemethyltubulosine (7), followed by selective 0-methylation of the ortho-phenolic hydroxy groups, could finally give tubulosine (8). On the other hand, the presence of a partial structure corresponding to that of the terpenoid indole alkaloids suggests an alternative pathway beginning with strictosidine (1) which is the universal precursor for terpenoid indole alkaloid^.^*^ However, this pathway is argued against by the close relationship of cephaeline (10) and tubulosine (8) in terms of structure, including stereochemical detail, their cooccurrence in A. lamarckii, and the fact that any biosynthetic route from strictosidine (1) to tubulosine (8) must involve inversion of stereochemistry at C-4' (biosynthetic label : C-15) of strictosidine (1). Thus hydrolysis of (1) followed by opening of the pyran ring and decarboxylation, could afford the dialdehyde (3).…”

mentioning

confidence: 99%

Biosynthesis of the ipecac β-carboline alkaloid tubulosine

Bhakuni¹,

Jain²,

Chaturvedi³

1983

J. Chem. Soc., Perkin Trans. 1

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confidence: 99%

Biosynthesis of the ipecac β-carboline alkaloid tubulosine

Bhakuni¹,

Jain²,

Chaturvedi³

1983

J. Chem. Soc., Perkin Trans. 1

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“…Tubulosine is first isolated from the bark of P. tubulosus in 1964 [11]. The detailed chemical properties of tubulosine and its antitumor activity were further evaluated following isolation from the sap of Pogonopus speciosus in the 1990s [2526].…”

Section: Discussionmentioning

confidence: 99%

“…Tubulosine is first isolated from the bark of Pogonopus tubulosus in 1964 [11]. Although the structure of tubulosine and how to isolate it have long been known, its biological and pharmacological functions have yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Anticancer Activity of Tubulosine through Suppression of Interleukin-6-Induced Janus Kinase 2/Signal Transducer and Activation of Transcription 3 Signaling

Kim

et al. 2019

J Breast Cancer

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PurposeThe chemical structure of tubulosine has been known since the mid-1960s. However, little is known about its biological and pharmacological functions. The aim of this study was to investigate the novel functions of tubulosine in cancer treatment, specifically in breast cancer.MethodsAn Unpaired (Upd)-induced Drosophila cell line and interleukin (IL)-6-stimulated human breast cancer cell lines were used to investigate the biological and pharmacological activities of tubulosine in vitro. To investigate the activities of tubulosine, we performed molecular and cellular experiments such as Western blot and reverse transcription polymerase chain reaction analyses, immunoprecipitation and terminal deoxynucleotidyl transferase dUTP nick end labeling assays, and immunofluorescence staining using breast cancer cell lines.ResultsTubulosine exhibited anticancer activity in IL-6-stimulated human breast cancer cells. Moreover, tubulosine reduced the tyrosine phosphorylation level and transcriptional activity of signal transducer and activator of transcription (STAT) protein at 92E in Upd-induced Drosophila cells. Additionally, tubulosine suppressed IL-6-induced Janus kinase 2 (JAK2)/STAT3 signaling, resulting in decreased viability and induction of apoptotic cell death in breast cancer cells. Interestingly, inhibition of IL-6-induced JAK2/STAT3 signaling by tubulosine was associated with the blocking of IL-6 receptor (IL-6R) and glycoprotein 130 (gp130) binding.ConclusionTubulosine exhibits anticancer activity through functional inhibition of IL-6-induced JAK2/STAT3 signaling by targeting IL-6Rα/gp130 binding in breast cancer cells. These findings suggest that tubulosine may hold promise for the treatment of inflammation-associated cancers, including breast cancer.

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“…2A). The remaining metabolites were mostly single species rather than metabolite groups, which could be food constituents present as additives, spices, or contaminants such as [6]-gingerdiol 5-O-beta-D-glucopyranoside, 35 guaiazulene, 36 tubulosine, 37 1,4-dinitrophenol, 38 or bacterial metabolites such as L-olivosyl oleandolide. 39 There were, however, a number of peptides comprising essential amino acids (Glu-Ile, His-Met-Leu, and Val-Tyr-Ile), whose difference between the groups (Non-PEN and PEN) could be relevant to the consumption of the formula.…”

Section: Impact Of Pen Treatmentmentioning

confidence: 99%

Metabolomic Signatures in Pediatric Crohn’s Disease Patients with Mild or Quiescent Disease Treated with Partial Enteral Nutrition: A Feasibility Study

Marques¹,

Shokry²,

Frivolt

et al. 2021

SLAS Technology

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Little is known about the metabolic response of pediatric Crohn’s disease (CD) patients to partial enteral nutrition (PEN) therapy and the impact of disease activity and inflammation. We analyzed plasma samples from a nonrandomized controlled intervention study investigating the effect of partial enteral nutrition (PEN) on bone health and growth throughout one year with untargeted metabolomics using high-performance liquid chromatography (HPLC) coupled with high-resolution mass spectrometry (HRMS). Thirty-four paired samples from two time points (baseline and 12 months) were analyzed. Patients (median age: 13.9 years, range: 7–18.9 years, 44% females) were in remission or had mild disease activity. The intervention group received a casein-based formula for 12 months, providing ~25% of estimated daily energy requirements. Sparse partial least squares discriminant analysis (splsda) was applied for group discrimination and identifying sources of variation to identify the impact of PEN. We also investigated the correlation of metabolites with inflammation markers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fecal calprotectin. After 12 months, our results show substantial difference between PEN and non-PEN groups in the metabolome of CD patients in remission or with mild disease activity. Inflammatory markers were associated with individual compounds and chemical classes such as isoprenoids and phospholipids. Identified compounds comprise metabolites produced by human or bacterial metabolism, as well as xenobiotics recognized as flavoring agents and environmental contaminants and their biotransformation products. Further longitudinal studies that also include patients with higher disease activity are warranted to evaluate the suitability of these metabolic biomarkers for predicting disease activity.

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The Structure of Tubulosine, a Novel Alkaloid from Pogonopus tubulosus (DC.) Schumann

Cited by 30 publications

References 0 publications

Biosynthesis of the ipecac β-carboline alkaloid tubulosine

Biosynthesis of the ipecac β-carboline alkaloid tubulosine

Anticancer Activity of Tubulosine through Suppression of Interleukin-6-Induced Janus Kinase 2/Signal Transducer and Activation of Transcription 3 Signaling

Metabolomic Signatures in Pediatric Crohn’s Disease Patients with Mild or Quiescent Disease Treated with Partial Enteral Nutrition: A Feasibility Study

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