Calycanthidine

DART-HRMS allows the detection of toxic alkaloids in animal autopsy specimens and guides the selection of confirmatory methods in accidental plant poisoning.[Pubmed:37230724]

Anal Chim Acta. 2023 Jul 11;1264:341309.

BACKGROUND: In cases of suspected animal poisonings or intoxications, there is the need for high-throughput, rapid and accurate analytical tools capable of giving rapid answers and, thus, speeding up the early stages of investigations. Conventional analyses are very precise, but do not meet the need for rapid answers capable of orienting the decisions and the choice of appropriate countermeasures. In this context, the use of ambient mass spectrometry (AMS) screening methods in toxicology laboratories could satisfy the requests of forensic toxicology veterinarians in a timely manner. RESULTS: As a proof of principle, direct analysis in real time high resolution mass spectrometry (DART-HRMS) was applied to a veterinary forensic case in which 12 of a group of 27 sheep and goats died with an acute neurological onset. Because of evidence in the rumen contents, the veterinarians hypothesized an accidental intoxication after ingestion of vegetable materials. The DART-HRMS results showed abundant signals of the alkaloids calycanthine, folicanthidine and Calycanthidine, both in the rumen content and at the liver level. The DART-HRMS phytochemical fingerprinting of detached Chimonanthus praecox seeds was also compared with those acquired from the autopsy specimens. Liver, rumen content and seed extracts were then subjected to LC-HRMS/MS analysis to gather additional insights and confirm the putative assignment of calycanthine anticipated by DART-HRMS. HPLC-HRMS/MS confirmed the presence of calycanthine in both rumen contents and liver specimens and allowed its quantification, ranging from 21.3 to 46.9 mg kg(-1) in the latter. This is the first report detailing the quantification of calycanthine in liver after a deadly intoxication event. SIGNIFICANCE AND NOVELTY: Our study illustrates the potential of DART-HRMS to offer a rapid and complementary alternative to guide the selection of confirmatory chromatography-MS(n) strategies in the analysis of autopsy specimens from animals with suspected alkaloid intoxication. This method offers the consequent saving of time and resources over those needed for other methods.

[Discrimination and clinical value of plasma metabolomic profiles in multidrug resistant epithelial ovarian cancer].[Pubmed:29262505]

Zhonghua Zhong Liu Za Zhi. 2017 Dec 23;39(12):896-902.

Objective: To explore the alteration of plasma metabolomic profiles, screen the new serum markers of multidrug resistant epithelial ovarian cancer (EOC), and investigate the mechanism. Methods: The serum of 132 cases with cisplatin-resistant EOC, cisplatin-sensitive EOC, benign ovarian cyst and healthy donors were collected. Differentially plasma metabolic profiles were identified by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The significantly different metabolites of each group were screened by using principal component analysis. Then compounds that played a key role in cisplatin resistance were identified by using nuclear magnetic resonance (NMR). The relationships between these compounds and clinical characteristics and prognosis were analyzed. Results: LC-MS/MS identified 25 800 metabolic compounds. According to the descending dimension algorithm by principal component analysis, six compounds which were the biggest contributor to grouping were identified. The identified results of NMR showed that the serum level of C16 Sphinganine was lower while Dodemorph was higher in the EOC than those of the normal control. Compared to the cisplatin sensitive group, cisplatin resistant group exhibited a specific metabolic trait characterized by upregulation of 1-Monopalmitin, Ricinoleic acid methyl ester, Polyoxyethylene (600) mono-ricinoleate/Glycidyl stearate and downregulation of Calycanthidine. The four components were all associated with fatty acid metabolism, and the combinational diagnostic sensitivity of these biomarkers for cisplatin-resistance was 86.50% and the specificity was 81.80%, the area of receiver operating characteristic (ROC) curve was 0.93. Conclusions: The metabolic signatures of normal control, benign ovarian cyst, cisplatin sensitivity and cisplatin resistance can be clearly separated from each other by LC-MS/MS technology.The combinational four biomarkers including Calycanthidine, 1-Monopalmitin, Ricinoleic acid methl ester and Polyoxyethylene (600) mono-ricinoleate/Glycidyl stearate are more sensitive and specific for the diagnosis of cisplatin resistant EOC, and may provide the potentially predict markers of chemotherapeutic response in metabolic level. The fatty acid metabolism may participate in the cisplatin resistant progression of EOC.

Dimeric pyrrolidinoindoline-type alkaloids with melanogenesis inhibitory activity in flower buds of Chimonanthus praecox.[Pubmed:24668298]

J Nat Med. 2014 Jul;68(3):539-49.

A methanol extract of the flower buds of Chimonanthus praecox (L.) Link (Calycanthaceae) demonstrated inhibitory effects on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. From the extract, five dimeric pyrrolidinoindoline alkaloids and four sesquiterpenes were isolated, together with 16 known compounds. Among them, (-)-chimonanthine (1, IC50 = 0.93 muM), (-)-folicanthine (2, 1.4 muM), and (-)-Calycanthidine (3, 1.8 muM) showed potent inhibitory effects without notable cytotoxicity at the effective concentrations. The most potent alkaloid (1) inhibited both tyrosinase and tyrosine-related protein-1 mRNA expressions, to which the melanogenesis inhibitory activity would be ascribable.

Application of diazene-directed fragment assembly to the total synthesis and stereochemical assignment of (+)-desmethyl-meso-chimonanthine and related heterodimeric alkaloids.[Pubmed:24409339]

Chem Sci. 2014 Jan 1;5(1):10.1039/C3SC52451E.

We describe the first application of our methodology for heterodimerization via diazene fragmentation towards the total synthesis of (-)-Calycanthidine, meso-chimonanthine, and (+)-desmethyl-meso-chimonanthine. Our syntheses of these alkaloids feature an improved route to C3a-aminocyclotryptamines, an enhanced method for sulfamide synthesis and oxidation, in addition to a late-stage diversification leading to the first enantioselective total synthesis of (+)-desmethyl-meso-chimonanthine and its unambiguous stereochemical assignment. This versatile strategy for directed assembly of heterodimeric cyclotryptamine alkaloids has broad implications for the controlled synthesis of higher order derivatives with related substructures.

[Chemical constituents from the seed of Chimonanthus praecox extracted by supercritical carbon dioxide].[Pubmed:18973012]

Zhong Yao Cai. 2008 Jul;31(7):992-5.

OBJECTIVE: To analyse the volatile oil from seed of Chimonanthus praecox. METHODS: The volatile oil was extracted by Supercritical CO2 fluid and was analysed by GC-MS. RESULTS: Through comparison with mass spectra database, 43 components were isolated and identified. The main components are Calycanathine (51.88%), Calycanthidine (11.43%), n-Pentatriacontene (11.49%), (E, E)-2,4-Decadienal (9.67%), 1,1-diethoxyethoxy-3, 7-dimethyl-2, 6-Octadiene ( 3.40%), 7, 10-Octadecadienoic acid, methyl ester (3.38% ), 2, 13-Octadecadien-1-ol (2.90%), (1S-cis)-1,2,3,5,6,8a-hexahydro-4,7-dimethyl-1 (1-methylethyl)-Naphthalene (1. 90%), 3-Hexadecyne ( 1.82%), Hexadecanoic acid metyl ester( 1.78% ), Caryophyllene oxide (1.49%), n-Hexadecanoic acid (1.48%), Spathulenol (1.07%). CONCLUSION: Compounds (1S-cis)-1, 2,3,5,6,8a-hexahydro-4,7-dimethyl-1-(1-metyl-ethyl)-Naphthalene, Farnesol and Spathulenol are isolated from the Chimonanthus praecox for the first time.