Clausine K

alpha-Glucosidase and Nitric Oxide Inhibitory Activities of Pyranocoumarins and Carbazoles From the Roots of Clausena excavata and the Semisynthetic Analogs of Clausarin and Nordentatin.[Pubmed:40720625]

Chem Biodivers. 2025 Nov;22(11):e00510.

Phytochemical investigation of the methanol extract of Clausena excavata roots led to the isolation of six pyranocoumarin derivatives, including xanthyletin (1), kinocoumarin (2), clausarin (3), nordentatin (4), dentatin (4a), and citrusarin A (5), and three carbazole alkaloids, that is, heptaphylline (6), 7-methoxymukonal (7), and Clausine K (8). Seven new semisynthetic analogs of compounds 2, 3, and 4 (2a, 3b-3d, and 4b-4d) were prepared through methylation, etherification, and basic hydrolysis for biological assays. Compounds 2, 6, 3b, 3c, 4b, and 4c displayed stronger alpha-glucosidase inhibitory activity than the positive control, acarbose (IC(50) 391.47 microM), with IC(50) values in the range of 32.89-92.55 microM. Molecular docking suggested that these compounds bind near the enzyme's active site via van der Waals forces, hydrogen bonds, and hydrophobic interactions. Compound 3 showed the strongest nitric oxide (NO) inhibitory activity (IC(50) = 27.95 microM), followed by 3d (IC(50) = 33.62 microM) and 4 (IC(50) = 35.41 microM). For the two compounds tested for cytotoxicity against A549 cells, 3b (IC(50) = 11.71 microM) was more potent than cisplatin (IC(50) = 21.56 microM), whereas 4b (IC(50) = 22.39 microM) showed similar activity to cisplatin. Drug-likeness and pharmacokinetic properties of the isolated and semisynthetic compounds were also evaluated.

Morphological and metabolic changes in Changshan Huyou (Citrus changshan-huyou) following natural tetraploidization.[Pubmed:40055582]

BMC Plant Biol. 2025 Mar 8;25(1):301.

BACKGROUND: Polyploids in citrus are generally used to improve crop varieties. Changshan Huyou (Citrus changshan-huyou) is a native citrus species in China that is highly adaptable and has pharmaceutical value. However, the influence in Changshan Huyou following polyploidization remains unclear. Here we evaluated the adult tetraploid scions of Changshan Huyou with contemporary diploid scions as the control in the phenotypic variations, metabolic alterations of fruits and associated transcriptomic changes. RESULT: The tetraploid scions had rounder and thicker leaves, larger floral organs and fruits, and satisfactory viability of pollen grains and ovules. The tetraploid fruits accumulated lower levels of soluble solids but similar levels of organic acids. Metabolic profiling of three tissues of fruits revealed that most of 2064 differentially accumulated metabolites (DAMs), including flavonoids, lignans, and coumarins, were downregulated. In contrast, the upregulated DAMs mainly included alkaloids (Clausine K and 2-(1-pentenyl)quinoline), amino acids (L-asparagine and L-ornithine), and terpenoids (deacetylnomilin and evodol) in tetraploid peels, as well as, flavonoids (neohesperidin and quercetin-5-O-beta-D-glucoside) and organic acids (2-methylsuccinic acid and dimethylmalonic acid) in juice sacs. The upregulated genes were associated with phenylpropanoid biosynthesis, secondary metabolite biosynthesis, and the biosynthesis of various alkaloid pathways. Pearson Correlation Analysis showed that the upregulated genes encoding PEROXIDASE and CYTOCHROME P450 (CYP450) were closely related to the higher accumulation of amino acids and alkaloids in tetraploid peels, and up-regulated neohesperidin and quercetin glucoside were positively associated with FERULATE-5-HYDROXYLASE (F5H), CYP450 81Q32, FLAVONOID 3'-MONOOXYGENASE (F3'H), 4-COUMARATE-CoA LIGASE 1 (4CL1), and UDP-GLUCOSE FLAVONOID 3-O-GLUCOSYLTRANSFERASE (UFOG), as well as, some transcription factors in tetraploid juice sacs. CONCLUSION: The tetraploid Changshan Huyou investigated here may be used in triploids breeding to produce seedless citrus, and for fruit processing on pharmaceutical purpose due to the alteration of metabolites following polyploidization.

Bio-Guided Isolation of Prospective Bioactive Constituents from Roots of Clausena indica (Dalzell) Oliv.[Pubmed:31817276]

Molecules. 2019 Dec 4;24(24):4442.

Clausena indica fruits are routinely used for the culinary purpose as natural spices, whereas leaves and roots are folk medicine with various health benefits in southern China, South and Southeast Asia. In this study, the bioassay-guided fractionation by column chromatography yielded three pure compounds including dentatin, nordentatin, and Clausine K and five active fractions (Re1-5) from C. indica roots. These known anticancer compounds were confirmed by X-ray diffraction, (1)H-, (13)C-nuclear magnetic resonance (NMR), and electrospray ionization tandem mass spectrometric (ESI-MS-MS) analyses. Meanwhile, the phytochemical constituents from fractions were identified by gas chromatography-mass spectrometry (GC-MS). The isolates, fractions' components and their biological activities were first time investigated on C. indica. By in vitro DPPH and ABTS scavenging assays, nordentatin (IC(50) = 49.2 and 69.9 microg/mL, respectively) and the fraction Re4 (32.4 and 38.5 microg/mL, respectively) showed the strongest antiradical activities, whereas Clausine K presented a moderate and dentatin had negligible antioxidant activity, respectively. The anti-alpha-amylase activity of C. indica root extracts was mainly attributed to the fraction Re2 which inactivated the enzymatic assay with IC(50) of 573.8 microg/mL. Among tested samples, only nordentatin and Clausine K were effective in the pancreatic elastase inhibition, however, their influences were trivial. Markedly, Clausine K and Re4 performed the most remarkable tyrosinase inhibition with IC(50) values of 179.5 and 243.8 microg/mL, respectively, which were in turn 4 and 3 times stronger than myricetin (IC(50) = 735.6 microg/mL), a well-known tyrosinase inhibitor. This is the first report affirming Clausine K to be a new strong tyrosinase inhibitor. Isolated compounds from C. indica roots were quantified by high-performance liquid chromatography (HPLC), of which, dentatin, nordentatin, and Clausine K accounted for 14.74, 6.14, and 1.28 mg/g dry weight. The findings suggest that bioactive constituents from C. indica roots may be potentially employed for the development of antidiabetic, antiaging and cosmetic agents.

Increased Carbazole Alkaloid Accumulation in Clausena harmandiana Callus Culture by Treatments of Biocontrol Agent, Trichoderma harzianum and Bacillus subtilis.[Pubmed:31140051]

Appl Biochem Biotechnol. 2019 Nov;189(3):871-883.

Clausena harmandiana (Pierre) Guillaumin is the Thai medicinal plant that possessed several pharmacological activities. The main active constituents of this plant are the carbazole alkaloids, isolated from wild plants. However, the in vitro culture for production of carbazole alkaloids from this plant has never been reported. Therefore, we aimed to develop callus culture of C. harmandiana elicited with two biotic elicitors, Trichoderma harzianum and Bacillus subtilis, as a sustainable source of carbazole alkaloids. The callus treated with living B. subtilis (BL) at 0.1 and 1% (v/v) for 3 days accumulated 5-fold increased level of Clausine K. The highest level reached 309.37 +/- 34.84 mug/g DW. This treatment also showed a significant increase in both total phenolic content and antioxidant capacity, which support the optimum usage of this elicitor. Moreover, only callus treated with 1% (v/v) Trichoderma culture filtrate (CF) showed a significant increase in the total phenolic contents and antioxidant capacity. The correlation analysis also revealed the significant correlation between antioxidant capacity and total phenolic level, total flavonoids, and Clausine K but not 7-methoxymukonal. The results from our study suggested the use of C. harmandiana callus with the Bacillus elicitors for high-level production of Clausine K.

Production of carbazole alkaloids through callus and suspension cultures in Clausena harmandiana.[Pubmed:30585087]

Nat Prod Res. 2020 Feb;34(3):434-440.

Carbazole alkaloids are major constituents in Clausena spp. and exhibit a wide range of biological activities. The roots of Clausena harmandiana are a rich source of active carbazole alkaloids. However, its roots take several years to grow to be able to harvest. To obtain an alternative source of carbazole alkaloids, in vitro callus cultures of C. harmandiana were induced, and the formation of two active carbazole alkaloids was investigated. The effects of precursor, concentrations of sucrose, elicitors and light were studied to improve carbazole alkaloids formation. In this study, light had a strong effect on the formation of both carbazole alkaloids. The highest yields of Clausine K and 7-methoxymukonal were 4.74 +/- 0.26 and 0.92 +/- 0.04 mg/g DW, respectively, which have more than 10-fold found in intact roots. According to the results of this study, C. harmandiana callus cultures can be used as an alternative source of carbazole alkaloids for additional biological studies.

Carbazole-pyranocoumarin conjugate and two carbazole alkaloids from the stems of Clausena excavata.[Pubmed:26824689]

Nat Prod Res. 2016 Aug;30(15):1690-7.

A carbazole-pyranocoumarin conjugate, carbazomarin B (1), and two carbazole alkaloids, 6-methoxymukonidine (2) and 2-hydroxy-3-methoxycarbazole (3), together with 27 known compounds (4-30), were isolated from the stems of Clausena excavata. Their structures have been elucidated by spectroscopic analyses. Compound 2 showed moderate cytotoxicity to HuCCA-1, MOLT-3 and HepG2 cancer cell lines with IC50 values of 15.09-28.50 mug/mL, but none to A549 cell line. Heptaphylline (6) and nordentatin (23) were found to show moderate cytotoxic activity against HepG2 cell line with IC50 values of 12.33 and 11.33, respectively, while Clausine K (27) exhibited strong cytotoxicity with IC50 value of 1.05 mug/mL, better than a standard drug (etoposide, IC50 13.40 mug/mL).

First total synthesis of the biologically active 2,7-dioxygenated tricyclic carbazole alkaloids 7-methoxy-O-methylmukonal, clausine H (clauszoline-C), clausine K (clauszoline-J) and clausine O.[Pubmed:16106290]

Org Biomol Chem. 2005 Sep 7;3(17):3099-101.

Using the iron-mediated arylamine cyclization as the key step we have achieved a short and highly efficient access to the biologically active 2,7-dioxygenated tricyclic carbazole alkaloids 7-methoxy-O-methylmukonal, clausine H (clauszoline-C), Clausine K (clauszoline-J) and clausine O.

Coumarins and carbazoles with antiplasmodial activity from Clausena harmandiana.[Pubmed:10821058]

Planta Med. 2000 Apr;66(3):277-9.

Activity guided fractionation of extracts from Clausena harmandiana have led to the identification of four known compounds, heptaphylline (1), Clausine K (2), dentatin (5), and clausarin (6). All these compounds, except Clausine K (2), exhibited antiplasmodial activity against Plasmodium falciparum. While the new dimethylated derivative 4, derived from 2, showed no antiplasmodial activity, the monomethylated product 3 (clausine H) exhibited activity comparable to that observed for compounds 1 and 5.

Clausine K (CAS 182261-96-7) is a natural product offered by BioCrick for research applications. Customers can buy or order Clausine K from BioCrick, a supplier and manufacturer of research chemicals, with product specifications, purity, packaging, and pricing information available upon request.