• Biomolecules & Therapeutics
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• v.32 no.5
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• pp.627-634
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• 2024

Sesquiterpene lactones, a class of natural compounds abundant in the Asteraceae family, have gained attention owing to their diverse biological activities, and particularly their anti-proliferative effects on human cancer cells. In this study, we systematically investigated the structure-activity relationship of ten sesquiterpene lactones with the aim of elucidating the structural determinants for the STAT3 inhibition governing their anti-proliferative effects. Our findings revealed a significant correlation between the STAT3 inhibitory activity and the anti-proliferative effects of sesquiterpene lactones in MDA-MB-231 breast cancer cell lines. Among the compounds tested, alantolactone and isoalantolactone emerged as the most potent STAT3 inhibitors, highlighting their potential as candidates for anticancer drug development. Through protein-ligand docking studies, we revealed the structural basis of STAT3 inhibition by sesquiterpene lactones, emphasizing the critical role of hydrogen-bonding interactions with key residues, including Arg609, Ser611, Glu612, and Ser613, in the SH2 domain of STAT3. Furthermore, our conformational analysis revealed the decisive role of the torsion angle within the geometry-optimized structures of sesquiterpene lactones in their STAT3 inhibitory activity (R=0.80, p<0.01). These findings not only provide preclinical evidence for sesquiterpene lactones as promising phytomedicines against diseases associated with abnormal STAT3 activation, but also highlight the importance of stereochemical aspects in their activity.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.369.1-369.1
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• 2002

In our previous study, the leaves of Ixeris sonchifolia afforded two new and two known guaiane type sesquiterpene lactones by activity-guided fractionation. Now we report additional isolation of sesquiterpene lactones from the roots of Ixeris sanchi!a!ia. They are glucozaluzanin C and ixerin H. Ixerin H is germacranolide type sesquiterpene glucuside. Theil structures were determined by 1 D and 2D NMR spectroscopy. (omitted)

• Journal of Plant Biology
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• v.16 no.1_2
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• pp.12-16
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• 1973

The inhibitory effect of Inula sesquiterpene lactones on the growth of Phaseolus vulgaris was tested and the abnormality of the stem organization caused by the lactones was also examined. The longitudinal growth of the young stem and the expansion of the young leaf were stopped by the application of the lactones. However, this inhibitory effect was appeared and strictly restricted within the treated area. So the young shoot was observed for possible bending as a result of the unilateral application of the lactones. When the application of the lactones into the medium, the growth of the plant was entirely repressed. However, the growth of shoot and re-initiation of root were started after the plant was transfered to the lactone free medium. And partial reversal of inhibition of the stem growth was achieved by the additions of gibberelline and the lactones.

• Journal of the Korean Society of Food Science and Nutrition
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• v.26 no.1
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• pp.144-147
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• 1997

For the investigation of antitumor agents, two kinds of sesquiterpene lactones were isolated and purified from Chrysanthemum boreale M. and designated as Compound I and ]U . And then in vivo antitumor test of the sesquiterpene lactones was carried out against ICR mice. In vivo test against Sarcoma180 implanted ICR mice, life prolongation effects of Compound I and II were showed as 143% and 134% at the dose of 10mg/kg, respectively. Besides, at the tested group mixed Compound I and II each 1mg/kg was showed rather high life prolongation effect as 158%.

• Applied Biological Chemistry
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• v.38 no.5
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• pp.473-477
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• 1995

The dichloromethane extracts of the above ground parts of Hymenoxys brachyactis afforded three sesquiterpene lactones already reported, one new sesquiterpene lactone, biennin C and hispidulin as known toxic flavone. Structures of all compounds were established by spectroscopy and biennin C was determined as an adduct of the modified pseudoguanolide and hymenoxon by Gas Chromatograpy and MS spectrometer These sesquiterpene lactones have the same ${\alpha},{\beta}$-unsaturated functional group like that of hymenovin which has been known as major toxic constituent of important livestock poison. And biennin C is also considered as toxic compound because of toxic hymenoxon.

• Korean Journal of Pharmacognosy
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• v.30 no.1
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• pp.70-73
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• 1999

Nine sesquiterpene lactones, which were isolated from Hemisteptia lyrata Bunge. Chrysanthemum zawadskii Herbich var. latilobum Kitamura and Chrysanthemum boreale Makino were evaluated for the farnesyl-protein transferase (FPTase) inhibitor, conducted by the scintillation proximity assay (SPA). The angeloylcumambrin B and tigloylcumambrin B inhibited a recombinant rat FPTase with $IC_{50}$ value of $78\;{\mu}g/ml$ $(225\;{\mu}M)$ and $90\;{\mu}g/ml$ $(260 \;{\mu}M)$, respectively.

• Natural Product Sciences
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• v.11 no.2
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• pp.55-57
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• 2005

Three known sesquiterpene lactones were isolated from the n-BuOH traction of the roots of Ixeris sonchifolia. Their structures were identified as macrocliniside A (1), glucozaluzanin C (2), and ixerin H (3), by spectral analyses. Compounds 1 and 2 are guaiane-type, while compound 3 is a germacrane-type sesquiterpene lactone. Compounds 1-3 are first isolated from I. sonchifolia.

• YAKHAK HOEJI
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• v.45 no.2
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• pp.147-152
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• 2001

The phytochemical study of the aerial parts of Artemisia sylvatica (Asteraceae) led to the isolation of nine sesquiterpene lactones, l$\alpha$-hydroperoxy-rupicolin A acetate (1), rupicolin B acetate (2), rupicolin A acetate (3), l$\alpha$-hydroxy-4$\alpha$-hydroperoxy-bishopsolicepolide (4), 1$\alpha$-hydroperoxy-4$\beta$-hydroxy-8$\alpha$-acetoxy-guaia-2,9,11 (13)-triene-6$\alpha$,12-oxide (5), 1$\alpha$-hydroperoxy-4$\alpha$-hydroxybishopsolicepolide (6), l$\alpha$,4$\beta$-dihydroxy-8$\alpha$-acetoxy-guaia-2,9,11(13)-triene-6$\alpha$,12-olive (7), rupicolin A (8) and l$\alpha$,4$\alpha$-dihydroxy-bishopsolicepolide (9). Their structures were established by chemical and spectroscopic methods.

• Archives of Pharmacal Research
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• v.28 no.10
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• pp.1142-1146
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• 2005

Seven sesquiterpene lactones were isolated by the chromatographic separation of the MeOH extract of the aerial parts of Saussurea calcicola (Compositae). Their structures were determined spectroscopically to be cynaropicrin (1), arguerin B (2), cebellin F (3), 8${\alpha}$-hydroxy-11${\alpha}$, 13-dihydrozaluzanin C (4), desacylcynaropicrin (5), 3${\beta}$-hydroxy-8${\alpha}$-epoxymethylacriloiloxy-4(15), 10(14), 11(13)-trien-guaian-6, 12-olide (6), and kandavanolide (7). Compounds 1 and 2 showed significant cytotoxicity against five cultured human tumor cell lines with $ED_{50}$ values ranging from $0.23{\~}1.72\;{\mu}g/mL$.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.6
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• pp.521-531
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• 2023

Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (E_max) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.