Sheng Yin

Name:

Organization: Sun Yat-Sen University

Department: School of Pharmaceutical Sciences

Title:

Chemicals
References

Design, Synthesis, and Biological Evaluation of Novel Selenium-Containing Isocombretastatins and Phenstatins as Antitumor Agents

Co-reporter:Yanqing Pang, Baijiao An, Lanlan Lou, Junsheng Zhang, Jun Yan, Ling Huang, Xingshu Li, and Sheng Yin

Journal of Medicinal Chemistry September 14, 2017 Volume 60(Issue 17) pp:7300-7300

Publication Date(Web):August 9, 2017

DOI:10.1021/acs.jmedchem.7b00480

Two series of structurally related organoselenium compounds designed by fusing the anticancer agent methyl(phenyl)selane into the tubulin polymerization inhibitors isocombretastatins or phenstatins were synthesized and evaluated for antiproliferative activity. Most of these selenium containing hybrids exhibited potent cytotoxicity against a panel of cancel cell lines, with IC50 values in the submicromolar concentration range. Among them, 11a, the 3-methylseleno derivative of isocombretastatin A-4 (isoCA-4) represented the most active compound with IC50 values of 2–34 nM against 12 cancer cell lines, including two drug-resistant cell lines. Importantly, its phosphate salt, 11ab, inhibited tumor growth in xenograft mice models with inhibitory rate of 72.9% without apparent toxicity, which was better than the reference compounds isoCA-4P (inhibitory rate 52.2%) and CA-4P (inhibitory rate 47.6%). Mechanistic studies revealed that 11a is a potent tubulin polymerization inhibitor, which could arrest cell cycle at G2/M phase and induce apoptosis along with the decrease of mitochondrial membrane potential. In summary, 11a could serve as a promising lead for the development of highly efficient anticancer agents.

Natural diarylfluorene derivatives: isolation, total synthesis, and phosphodiesterase-4 inhibition

Co-reporter:Jun-Sheng Zhang;Xin Liu;Jiang Weng;Yan-Qiong Guo;Qing-Jiang Li;Abrar Ahmed;Gui-Hua Tang

Organic Chemistry Frontiers 2017 vol. 4(Issue 2) pp:170-177

Publication Date(Web):2017/02/01

DOI:10.1039/C6QO00623J

In our previous study, selaginpulvilins A–D (1–4) featuring an unprecedented 9,9-diphenyl-1-(phenylethynyl)-9H-fluorene skeleton were identified as potent phosphodiesterase-4 (PDE4) inhibitors from Selaginella pulvinata. In the current work, a large-scale reinvestigation of the same plant led to the isolation of six additional new analogues, selaginpulvilins E–J (5–10), among which 5 features a rare 6-(4-hydroxyphenyl)-2H-pyran-2-one unit. Compounds 5–10 exhibited remarkable inhibitory activities against PDE4 with IC50 values in the range of 0.22–1.38 μM. The first total synthesis of selaginpulvilins A–F (1–6) was developed in 7–11 steps involving a Friedel–Crafts reaction as the key reaction, which provides a feasible access to this scaffold.

The discovery, complex crystal structure, and recognition mechanism of a novel natural PDE4 inhibitor from Selaginella pulvinata

Co-reporter:Yiyou Huang, Xin Liu, Deyan Wu, Guihua Tang, ... Hai-Bin Luo

Biochemical Pharmacology 2017 Volume 130(Volume 130) pp:

Publication Date(Web):15 April 2017

DOI:10.1016/j.bcp.2017.01.016

Phosphodiesterase-4 (PDE4) is an important drug target for treatment of inflammation-related diseases. Till now, natural PDE4 inhibitors are rare and their co-crystal structures with PDE4 are hardly available. In the present study, selaginpulvilins K and L (1 and 2), two novel fluorene derivatives, were isolated from a traditional Chinese medicine Selaginella pulvinata and exhibited remarkable inhibition against phosphodiesterase-4D (PDE4D) at IC50 11 nM and 90 nM, respectively. Compound 1 also showed a good selectivity across PDE families with the selective fold ranging from 30 to 909. To understand the recognition mechanism of selaginpulvilins towards PDE4, the crystal structure of PDE4D bound with 1 was successfully determined by the X-ray diffraction method and presented an unusual binding mode in which the stretched skeleton of the inhibitor bound shallowly to the active site but had interactions with multi sub-pockets, such as Q, HC, M, and S, especially strong interaction with the metal region. Assisted with molecular modeling, the structure–activity relationship and the selectivity of selaginpulvilins were also well explored, which would facilitate the future rational inhibitor design or structural optimizations.Download high-res image (260KB)Download full-size image

Bioactive diterpenoids from Croton laevigatus

Co-reporter:Jun-Sheng Zhang, Ya-Qi Tang, Jia-Luo Huang, Wei Li, Yi-Hong Zou, Gui-Hua Tang, Bo Liu, Sheng Yin

Phytochemistry 2017 Volume 144(Volume 144) pp:

Publication Date(Web):1 December 2017

DOI:10.1016/j.phytochem.2017.09.003

•Eight previously undescribed diterpenoids were isolated from Croton laevigatus.•Their absolute configurations were determined by extensive methods.•Two compounds are the first halimanes with a lactone bridge between C-12 and C-17.•Some compounds exhibited significant inhibitory activity on NO production.Eight previously undescribed diterpenoids, crolaevinoids A−H, including two halimanes, four clerodanes, and two laevinanes, along with six known analogues were isolated from the twigs of Croton laevigatus. The structures of the previously undescribed were elucidated by spectroscopic analysis, and their absolute configurations were determined by combination of a single crystal X-ray diffraction and CD analysis (exciton chirality and Rh2(OCOCF3)4-induced methods). Crolaevinoids A and B represent the first halimane diterpenoids with a unique lactone bridge between C-12 and C-17. All compounds were evaluated for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophage cells. Furocrotinsulolide A and 3,4,15,16-diepoxy-cleroda-13(16),14-diene-12,17-olide exhibited pronounced inhibition of NO production with IC50 values of 10.4 ± 0.8 and 6.0 ± 1.0 μM, respectively, being more potent than the positive control, quercetin (IC50 = 13.1 ± 1.9 μM).Eight previously undescribed diterpenoids along with six known analogues were isolated from the twigs of Croton laevigatus. Two compounds exhibited pronounced inhibition on LPS-induced NO production in RAW264.7 macrophage cells.Download high-res image (368KB)Download full-size image

Jatrophane Diterpenoids as Modulators of P-Glycoprotein-Dependent Multidrug Resistance (MDR): Advances of Structure–Activity Relationships and Discovery of Promising MDR Reversal Agents

Co-reporter:Jianyong Zhu; Ruimin Wang; Lanlan Lou; Wei Li; Guihua Tang; Xianzhang Bu

Journal of Medicinal Chemistry 2016 Volume 59(Issue 13) pp:6353-6369

Publication Date(Web):June 21, 2016

DOI:10.1021/acs.jmedchem.6b00605

The phytochemical study of Pedilanthus tithymaloides led to the isolation of 13 jatrophane diterpenoids (1–13), of which eight (1–8) are new. Subsequent structural modification of the major components by esterification, hydrolysis, hydrogenation, or epoxidation yielded 22 new derivatives (14–35). Thus, a jatrophane library containing two series of compounds was established to screen for P-glycoprotein (Pgp)-dependent MDR modulators. The activity was evaluated through a combination of Rho123 efflux and chemoreversal assays on adriamycin resistant human hepatocellular carcinoma cell line HepG2 (HepG2/ADR) and adriamycin resistant human breast adenocarcinoma cell line MCF-7 (MCF-7/ADR). Compounds 19, 25, and 26 were identified as potent MDR modulators with greater chemoreversal ability and less cytotoxicity than the third-generation drug tariquidar. The structure–activity relationship (SAR) was discussed, which showed that modifications beyond just increasing the lipophilicity of this class of Pgp inhibitors are beneficial to the activity. Compound 26, which exhibited a remarkable metabolic stability in vitro and a favorable antitumor effect in vivo, would serve as a promising lead for the development of new MDR reversal agents.

Chlojaponilactone B from Chloranthus japonicus: Suppression of Inflammatory Responses via Inhibition of the NF-κB Signaling Pathway

Co-reporter:Jing-Jun Zhao, Yan-Qiong Guo, De-Po Yang, Xue Xue, Qin Liu, Long-Ping Zhu, Sheng Yin, and Zhi-Min Zhao

Journal of Natural Products 2016 Volume 79(Issue 9) pp:2257-2263

Publication Date(Web):September 2, 2016

DOI:10.1021/acs.jnatprod.6b00355

Bioassay-guided fractionation of an ethanolic extract of Chloranthus japonicus led to the isolation of the known lindenane-type sesquiterpenoid chlojaponilactone B (1). This compound exhibited pronounced inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Further anti-inflammatory assays showed that 1 suppressed the levels of some key inflammation mediators, such as iNOS, TNF-α, and IL-6, in a dose-dependent manner, and reduced the ear thickness and neutrophil infiltration in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated mice. A mechanistic study revealed that compound 1 exerted its anti-inflammatory effects via the suppression of the NF-κB signaling pathway, which inhibited NF-κB-dependent transcriptional activity, IκBα phosphorylation, and p65 nuclear translocation. In contrast, chlojaponilactone B (1) was found to exert little influence on the MAPK signaling pathway.

Discovery and modelling studies of natural ingredients from Gaultheria yunnanensis (FRANCH.) against phosphodiesterase-4

Co-reporter:Ying-Hong Cai, Yanqiong Guo, Zhe Li, Deyang Wu, Xiruo Li, Heng Zhang, Junjie Yang, Heng Lu, Zhaowei Sun, Hai-Bin Luo, Sheng Yin, Yinuo Wu

European Journal of Medicinal Chemistry 2016 Volume 114() pp:134-140

Publication Date(Web):23 May 2016

DOI:10.1016/j.ejmech.2015.12.002

•13 compounds were isolated from Gaultheria yunnanensis (FRANCH.).•The pentacyclic triterpene (G1) was first reported and exhibited moderate selectivity over other PDE families.•The calculated binding free energies results are in consistence with the bioassay.Phosphodiesterase-4 (PDE4) is an anti-inflammatory target for treatment of asthma and chronic obstructive pulmonary disease (COPD). Here, we report the isolation and characterization of 13 compounds (G1-G13) by bioassay-guided fractionation of the ethyl acetate extraction of Gaultheria yunnanensis (FRANCH.), one of which pentacyclic triterpene (G1) has never been reported. Four of them (G1, G2, G4, and G5) inhibit PDE4 with the IC50 values < 20 μM and G1 is the most potent ingredient with an IC50 of 245 nM and moderate selectivity over other PDE families. Molecular dynamics simulations suggest that G1 forms a hydrogen bond with Asn362, in addition to the hydrogen bond with Gln369 and π-π interactions with Phe372, which are commonly observed in the binding of most PDE4 inhibitors. The calculated binding free energies for the interactions of PDE4-G1 and PDE4-G2 are −19.4 and −18.8 kcal/mol, in consistence with the bioassay that G1 and G2 have IC50 of 245 nM and 542 nM, respectively. The modelling results of these active compounds may aid the rational design of novel PDE4 inhibitors as anti-inflammatory agents.

Neolignans from Aristolochia fordiana Prevent Oxidative Stress-Induced Neuronal Death through Maintaining the Nrf2/HO-1 Pathway in HT22 Cells

Co-reporter:Gui-Hua Tang, Zi-Wei Chen, Ting-Ting Lin, Min Tan, Xiao-Yun Gao, Jing-Mei Bao, Zhong-Bin Cheng, Zhang-Hua Sun, Gang Huang, and Sheng Yin

Journal of Natural Products 2015 Volume 78(Issue 8) pp:1894-1903

Publication Date(Web):July 30, 2015

DOI:10.1021/acs.jnatprod.5b00220

Bioassay-guided fractionation of the ethanolic extract of the stems of Aristolochia fordiana led to the isolation of six new dihydrobenzofuran neolignans (1–3 and 7–9), three new 2-aryldihydrobenzofurans (4–6), a new 8-O-4′ neolignan (10), and 14 known analogues (11–24). The structures of compounds 1–10 were established by spectroscopic methods, and their absolute configurations were determined by analyses of the specific rotation and electronic circular dichroism data. The neuroprotective effects of compounds 1–24 against glutamate-induced cell death were tested in hippocampal neuronal cell line HT22. Compounds 17 and 20–24 exhibited moderate neuroprotective activity by increasing the endogenous antioxidant defense system. In addition, the neolignans activated the Nrf2 (nuclear factor E2-related factor 2) pathway, resulting in the increase of the expression of endogenous antioxidant protein HO-1 (heme oxygenase-1). The active compounds also preserved the levels of antiapoptotic protein Bcl-2 (B cell lymphoma/leukemia-2), which was decreased by glutamate. Collectively, these results suggested that the active neolignans protect neurons against glutamate-induced cell death through maintaining the Nrf2/HO-1 signaling pathway as well as preserving the Bcl-2 protein and might be promising novel beneficial agents for oxidative stress-associated diseases.

Enantiomeric neolignans and sesquineolignans from Jatropha integerrima and their absolute configurations

Co-reporter:Jian-Yong Zhu, Bao Cheng, Yin-Jia Zheng, Zhen Dong, Shu-Ling Lin, Gui-Hua Tang, Qiong Gu and Sheng Yin

RSC Advances 2015 vol. 5(Issue 16) pp:12202-12208

Publication Date(Web):14 Jan 2015

DOI:10.1039/C4RA15966G

Two pairs of new sesquineolignan enantiomers, (±)-jatrointelignans A and B (1a/1b and 2a/2b), one pair of new neolignan enantiomers, (±)-jatrointelignan D (4a/4b), and two new neolignans, (+)-jatrointelignan C (3a), and (+)-schisphenlignan I (5a) together with seven known analogues (3b, 5b, 6a, 6b, 7a, 7b, and 8) were isolated from the trunks of Jatropha integerrima. The structures were determined by combined spectroscopic and chemical methods, and their absolute configurations were elucidated by the circular dichroism (CD) method, in particular the configurations of the aryl glycerol-7′′,8′′-yloxy moiety in 1 and 2 were determined via the Rh2(OCOCF3)4-induced CD analysis. All compounds were examined for their inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in BV-2 microglial cells, and compounds 5a, 6a, and 4b exhibited pronounced inhibition on NO production with IC50 values in the range of 5.9–8.9 μM, being more active than the positive control, quercetin (IC50 = 17.0 μM).

Chlojapolactone A, an unprecedented 1,3-dioxolane linked-lindenane sesquiterpenoid dimer from Chloranthus japonicus

Co-reporter:Yan-Qiong Guo, Gui-Hua Tang, Zhen-Zhen Li, Shu-Ling Lin and Sheng Yin

RSC Advances 2015 vol. 5(Issue 125) pp:103047-103051

Publication Date(Web):25 Nov 2015

DOI:10.1039/C5RA22145E

Chlojapolactone A (1), a novel lindenane sesquiterpenoid dimer with an unprecedented 1,3-dioxolane linkage, was isolated from Chloranthus japonicus. Its structure and absolute configuration was elucidated by combined spectral, computational, and chemical approaches. Compound 1 exhibited potential inhibitory effects on nitric oxide production in RAW 264.7 cells.

Jatrocurcadiones A and B: two novel diterpenoids with an unusual 10,11-seco-premyrsinane skeleton from Jatropha curcas

Co-reporter:Jing-Mei Bao, Zhi-You Su, Lan-Lan Lou, Jian-Yong Zhu, Gui-Hua Tang, Li-She Gan, Xian-Zhang Bu and Sheng Yin

RSC Advances 2015 vol. 5(Issue 77) pp:62921-62925

Publication Date(Web):13 Jul 2015

DOI:10.1039/C5RA11380F

Two novel diterpenoids, jatrocurcadiones A (1) and B (2), possessing an unusual 10,11-seco-premyrsinane skeleton were isolated from the twigs of Jatropha curcas. Their structures were determined by combined spectroscopic and chemical methods, and the absolute configurations were elucidated by quantum chemical calculations and Rh2(OCOCF3)4-induced CD analysis. Jatrocurcadione A exhibited more potent inhibitory activity (IC50 = 10.0 μM) than the positive control (curcumin, IC50 = 25.0 μM) against thioredoxin reductase (TrxR), a potential target for cancer chemotherapy with redox balance and antioxidant functions.

Natural thioredoxin reductase inhibitors from Jatropha integerrima

Co-reporter:Jian-Yong Zhu, Lan-Lan Lou, Yan-Qiong Guo, Wei Li, Yan-Hong Guo, Jing-Mei Bao, Gui-Hua Tang, Xian-Zhang Bu and Sheng Yin

RSC Advances 2015 vol. 5(Issue 58) pp:47235-47243

Publication Date(Web):20 May 2015

DOI:10.1039/C5RA07274C

Nine new diterpenoids, jatrointelones A–I (1–9), including seven lathyranes (1–7) and two jatropholanes (8 and 9), along with 12 known analogues (10–21) were isolated from the trunks of Jatropha integerrima. The structures were elucidated by spectroscopic analysis, and the absolute configurations of 1–7 were determined by combination of single crystal X-ray diffraction, CD analysis (exciton chirality and Rh2(OCOCF3)4-induced methods), and chemical correlations. All of the isolates were screened for inhibitory activity against thioredoxin reductase (TrxR), which is a potential target for cancer chemotherapy with redox balance and antioxidant functions. Compounds 1, 3, 6, 7, and 15–21 exhibited stronger activity than the positive control, curcumin (IC50 = 25.0 μM), in which 17 and 19 represented the most active compounds with IC50 values of 9.4 and 6.8 μM, respectively. The active diterpenoids represent the rare examples of non-aromatic TrxR inhibitors from nature, and a preliminary structure–activity relationship is also proposed.

Isolation and cytotoxicity evaluation of taxanes from the barks of Taxus wallichiana var. mairei

Co-reporter:Zhang-Hua Sun, Yu Chen, Yan-Qiong Guo, Jie Qiu, Cui-Ge Zhu, Jing Jin, Gui-Hua Tang, Xian-Zhang Bu, Sheng Yin

Bioorganic & Medicinal Chemistry Letters 2015 Volume 25(Issue 6) pp:1240-1243

Publication Date(Web):15 March 2015

DOI:10.1016/j.bmcl.2015.01.056

Fifteen taxanes (1–15) including a new taxane glucoside, 7β,9α,10β-triacetoxy-13α-hydroxy-5α-O-(β-d-glucopyranosyl)taxa-4(20),11-diene (1), were isolated from the barks of Taxus wallichiana var. mairei. Compounds 1–15 representing three sub-types of 6/8/6-taxane were evaluated in vitro for anti-proliferative activity against a panel of parental and drug-resistant cancer cells. Potent compounds were found while several exhibited selective cytotoxicity. Especially, 3, 8, and 10 showed selective inhibition to breast carcinoma cell line MCF-7, while 13 selectively inhibited taxol resistant human ovarian carcinoma cell line A2780/TAX (IC50 = 0.19 μM), being more potent than the clinical drugs taxol (IC50 = 4.4 μM) and docetaxol (IC50 = 0.42 μM), and less cytotoxic to mouse embryonic fibroblast cell line NIH-3T3, a cell line close to normal cell line. The possible P-glycoprotein evasion mechanism of 13 against A2780/TAX and the preliminary structure–activity relationships (SARs) of this group of compounds were also discussed.

Antioxidative Cassane Diterpenoids from the Seeds of Caesalpinia minax

Co-reporter:Jun-Sheng Zhang;Yan-Qiong Guo;Jing-Mei Bao;Min-Hong Jiang;Shu-Ling Lin;Zhi-You Su;Gui-Hua Tang

Helvetica Chimica Acta 2015 Volume 98( Issue 10) pp:1387-1394

Publication Date(Web):

DOI:10.1002/hlca.201500230

Abstract

Five new cassane diterpenoids, caesalmins I–M (1–5), and 23 known analogs were isolated from the seeds of Caesalpinia minax. Their structures were elucidated by spectroscopic methods and comparison with reported data. The antioxidant properties of 1–28 were determined by the method of oxygen radical absorbance capacity of fluorescein (ORAC-FL), and 14 compounds exhibited good antioxidant activities with ORAC-FL values of 2.24–4.89 Trolox equivalents. The structureactivity relationship of the active compounds was also discussed.

Selaginpulvilins A–D, New Phosphodiesterase-4 Inhibitors with an Unprecedented Skeleton from Selaginella pulvinata

Co-reporter:Xin Liu, Hai-Bin Luo, Yi-You Huang, Jing-Mei Bao, Gui-Hua Tang, Yun-Yun Chen, Jun Wang, and Sheng Yin

Organic Letters 2014 Volume 16(Issue 1) pp:282-285

Publication Date(Web):December 12, 2013

DOI:10.1021/ol403282f

Selaginpulvilins A–D (1–4), four new phenols with an unprecedented 9,9-diphenyl-1-(phenylethynyl)-9H-fluorene skeleton, together with four known selaginellins (5–8) were isolated from Selaginella pulvinata. Their structures were elucidated by spectroscopic analysis and chemical correlation. The structure of 1 was confirmed by single-crystal X-ray diffraction. Compounds 1–8 exhibited remarkable inhibitory activities (IC50 values in the range of 0.11–5.13 μM) against phosphodiesterase-4 (PDE4), a drug target for the treatment of asthma and chronic obstructive pulmonary disease.

(±)-Torreyunlignans A–D, Rare 8–9′ Linked Neolignan Enantiomers as Phosphodiesterase-9A Inhibitors from Torreya yunnanensis

Co-reporter:Zhong-Bin Cheng ; Xiao Lu ; Jing-Mei Bao ; Qing-Hua Han ; Zhen Dong ; Gui-Hua Tang ; Li-She Gan ; Hai-Bin Luo

Journal of Natural Products 2014 Volume 77(Issue 12) pp:2651-2657

Publication Date(Web):December 12, 2014

DOI:10.1021/np500528u

(±)-Torreyunlignans A–D (1a/1b–4a/4b), four pairs of new 8–9′ linked neolignan enantiomers featuring a rare (E)-2-styryl-1,3-dioxane moiety, were isolated from the trunk of Torreya yunnanensis. The structures were determined by combined spectroscopic and chemical methods, and the absolute configurations were elucidated by ECD calculations. The compounds were screened by using tritium-labeled adenosine 3′,5′-cyclic monophosphate ([3H]-cGMP) as a substrate for inhibitory affinities against phosphodiesterase-9A (PDE9A), which is a potential target for the treatment of diabetes and Alzheimer’s disease. All of the enantiomers exhibited inhibition against PDE9A with IC50 values ranging from 5.6 to 15.0 μM. This is the first report of PDE9A inhibitors from nature.

Prostaglandin Derivatives: Nonaromatic Phosphodiesterase-4 Inhibitors from the Soft Coral Sarcophyton ehrenbergi

Co-reporter:Zhong-Bin Cheng ; Ya-Lin Deng ; Cheng-Qi Fan ; Qing-Hua Han ; Shu-Ling Lin ; Gui-Hua Tang ; Hai-Bin Luo

Journal of Natural Products 2014 Volume 77(Issue 8) pp:1928-1936

Publication Date(Web):July 30, 2014

DOI:10.1021/np500394d

Ten new prostaglandin derivatives (PGs), sarcoehrendins A–J (1–10), together with five known analogues (11–15) were isolated from the soft coral Sarcophyton ehrenbergi. Compounds 4–8 represented the first examples of PGs featuring an 18-ketone group. The structures including the absolute configurations were elucidated on the basis of spectroscopic analysis and chemical evidence. All of the isolates and six synthetic analogues (3a, 3b, 4a, and 11a–11c) were screened for inhibitory activity against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease. Compounds 2, 10, 11a, 11b, and 13–15 exhibited inhibition with IC50 values less than 10 μM, and compound 15 (IC50 = 1.4 μM) showed comparable activity to the positive control rolipram (IC50 = 0.60 μM). The active natural PGs (2, 10, and 13–15) represent the first examples of PDE4 inhibitors without an aromatic moiety, and a preliminary structure–activity relationship is also proposed.

Prenylated Coumarins: Natural Phosphodiesterase-4 Inhibitors from Toddalia asiatica

Co-reporter:Ting-Ting Lin ; Yi-You Huang ; Gui-Hua Tang ; Zhong-Bin Cheng ; Xin Liu ; Hai-Bin Luo

Journal of Natural Products 2014 Volume 77(Issue 4) pp:955-962

Publication Date(Web):March 5, 2014

DOI:10.1021/np401040d

Bioassay-guided fractionation of the ethanolic extract of the roots of Toddalia asiatica led to the isolation of seven new prenylated coumarins (1–7) and 14 known analogues (8–21). The structures of 1–7 were elucidated by spectroscopic analysis, and their absolute configurations were determined by combined chemical methods and chiral separation analysis. Compounds 1–5, named toddalin A, 3‴-O-demethyltoddalin A, and toddalins B–D, represent an unusual group of phenylpropenoic acid-coupled prenylated coumarins. Compounds 1–21 and four modified analogues, 10a, 11a, 13a, and 17a, were screened by using tritium-labeled adenosine 3′,5′-cyclic monophosphate ([3H]-cAMP) as substrate for their inhibitory activity against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease. Compounds 3, 8, 10, 10a, 11, 11a, 12, 13, 17, and 21 exhibited inhibition with IC50 values less than 10 μM. Toddacoumalone (8), the most active compound (IC50 = 0.14 μM), was more active than the positive control, rolipram (IC50 = 0.59 μM). In addition, the structure–activity relationship and possible inhibitory mechanism of the active compounds are also discussed.

Natural nitric oxide (NO) inhibitors from Aristolochia mollissima

Co-reporter:Zhen Dong, Qiong Gu, Bao Cheng, Zhong-Bin Cheng, Gui-Hua Tang, Zhang-Hua Sun, Jun-Sheng Zhang, Jing-Mei Bao and Sheng Yin

RSC Advances 2014 vol. 4(Issue 98) pp:55036-55043

Publication Date(Web):16 Oct 2014

DOI:10.1039/C4RA09612F

Six new sesquiterpenoids, aristomollins A–F (1–6), and 24 known analogues (7–30) were isolated from the leaves and stems of Aristolochia mollissima. Their structures were elucidated by spectroscopic analysis, and the absolute configurations of compounds 2–5 were determined by the chemical correlations and quantum chemical ECD calculations. Compound 1 represented an unprecedented 5,6-seco-4,5-cyclohumulane skeleton. All the compounds were examined for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in BV-2 microglial cells, and compounds 4, 9, 28, and 30 exhibited pronounced inhibition of NO production with IC50 values in the range of 5.7–9.9 μM, being more active than the positive control, quercetin (IC50 = 15.7 μM).

Four new cembranoids from the soft coral Sarcophyton sp.

Co-reporter:Zhong-Bin Cheng;Qiong Liao;Ye Chen;Cheng-Qi Fan;Zhi-Ying Huang;Xin-Jun Xu

Magnetic Resonance in Chemistry 2014 Volume 52( Issue 9) pp:515-520

Publication Date(Web):

DOI:10.1002/mrc.4108

First page of article

Determination of the Absolute Stereochemistry of Two New Aristophyllene Sesquiterpenes: A Combined Theoretical and Experimental Investigation

Co-reporter:Rui-Bo Wu;Zhong-Bin Cheng;Qing-Hua Han;Ting-Ting Lin;Jing-Wei Zhou;Gui-Hua Tang

Chirality 2014 Volume 26( Issue 4) pp:189-193

Publication Date(Web):

DOI:10.1002/chir.22294

ABSTRACT

Aristoyunnolins G (1) and H (2), two new diastereoisomeric sesquiterpenes featuring a rare aristophyllene skeleton, were isolated from the traditional Chinese medicine Aristolochia yunnanensis. Their absolute stereochemistry involving three chiral centers was determined by combined chemical, spectral, and Density Functional Theory (DFT) calculation methods. Chirality 26:189–193, 2014. © 2014 Wiley Periodicals, Inc.

Determination of the Absolute Configuration of Two Pairs of C-8C-9 Linked Neolignan Enantiomers

Co-reporter:Jing-Mei Bao;Zhong-Bin Cheng;Jun-Sheng Zhang;Jian-Yong Zhu;Gui-Hua Tang;Li-She Gan

Chirality 2014 Volume 26( Issue 12) pp:825-828

Publication Date(Web):

DOI:10.1002/chir.22395

ABSTRACT

Two pairs of new neolignan enantiomers, (±)-torreyayunan A (1a/1b) and (±)-torreyayunan B (2a/2b), featuring a rare C-8 − C-9′ linked skeleton, were isolated from leaves and twigs of Torreya yunnanensis. Their absolute configuration involving two chiral centers was determined by combined spectral and Density Functional Theory (DFT) calculation. This is the first report of the absolute configuration of this group of neolignans. Chirality 26:825–828, 2014. © 2014 Wiley Periodicals, Inc.

Extracellular Signal-Regulated Kinases (ERK) Inhibitors from Aristolochia yunnanensis

Co-reporter:Zhong-Bin Cheng, Wei-Wei Shao, Ye-Na Liu, Qiong Liao, Ting-Ting Lin, Xiao-Yan Shen, and Sheng Yin

Journal of Natural Products 2013 Volume 76(Issue 4) pp:664-671

Publication Date(Web):April 9, 2013

DOI:10.1021/np300887d

Six new sesquiterpenoids, aristoyunnolins A–F (1–6), an artifact of isolation [7-O-ethyl madolin W (7)], and 12 known analogues were isolated from stems of Aristolochia yunnanensis. The structures were determined by combined chemical and spectral methods, and the absolute configurations of compounds 2, 3, 5–7, 9, 14, and 17 were determined by the modified Mosher’s method and CD analysis. Compounds 1–19 were screened using a bioassay system designed to evaluate the effect on mitogen-activated protein kinases (MAPKs) signaling pathways. Among three MAPKs (ERK1/2, JNK, and p38), compounds 1, 4, 10–13, 16, 18, and 19 exhibited selective inhibition of the phosphorylation of ERK1/2. Compounds 16 and 19 were more active than the positive control PD98059, a known inhibitor of the ERK1/2 signaling pathway.

Chemical constituents from the ascidian Aplidium constellatum

Co-reporter:Qing-Hua Han, Cheng-Qi Fan, Ya-Nan Lu, Jin-Ping Wu, Xin Liu, Sheng Yin

Biochemical Systematics and Ecology 2013 Volume 48() pp:6-8

Publication Date(Web):June 2013

DOI:10.1016/j.bse.2012.11.014

Chemical investigation of the South China Sea ascidian Aplidium constellatum has led to the isolation of four sterols (1–4), two carboline alkaloids (5 and 6), a ceramide (7), two furanone derivatives (8 and 9), and six nucleosides (10–15). Compounds 1–3 and 5–9 were isolated from the family Polyclinidae for the first time and compounds 1–3 and 7 were considered as the chemotaxonomic markers for the species A. constellatum.Highlights► The chemistry of the South China Sea ascidian Aplidium constellatum has been reported. ► Eight isolated compounds were present in the family Polyclinidae for the first time. ► Four compounds were considered as chemotaxonomic markers for this species.

Unusual Guaiane Sesquiterpenoids from Artemisia rupestris

Co-reporter:Zhi-Yong Xie;Ting-Ting Lin;Mei-Cun Yao;Jin-Zhi Wan

Helvetica Chimica Acta 2013 Volume 96( Issue 6) pp:1182-1187

Publication Date(Web):

DOI:10.1002/hlca.201200408

Abstract

Two new guaiane sesquiterpenoids, (1β,5β)-1-hydroxyguaia-4(15),11(13)-dieno-12,5-lactone (1) and 1,5-epoxy-4-hydroxyguai-11(13)-en-12-oic acid (2), together with five known compounds, rupestonic acid (3), strobilactone A (4), antiquorin (5), isosclerone (6), and 5-hydroxy-2′,3′,4′,7,8-pentamethoxyflavone (7), were isolated from a 95% EtOH extract of Artemisia rupestris. Compounds 1 and 2 are rare examples of guaiane sesquiterpenoids, incorporating a 12,5-lactone group or featuring a 1,5-epoxy ring, respectively. The structures of 1 and 2 were identified by various spectroscopic methods. Compounds 1, 4, and 5 exhibited moderate cytotoxic activities against the human lung cancer 95-D cell line with IC₅₀ values of 11.3, 19.8, and 34.5 μM, respectively.

Neuroprotective polyhydroxypregnane glycosides from Cynanchum otophyllum

Co-reporter:Zhi-Min Zhao, Zhang-Hua Sun, Mei-Hui Chen, Qiong Liao, Ming Tan, Xin-Wen Zhang, Han-Dong Zhu, Rong-Biao Pi, Sheng Yin

Steroids (October 2013) Volume 78(Issue 10) pp:1015-1020

Publication Date(Web):1 October 2013

DOI:10.1016/j.steroids.2013.06.007

Highlights•Five new polyhydroxypregnane glycosides were isolated from Cynanchum otophyllum.•Structures were established by spectroscopic methods and acid hydrolysis.•Three compounds exhibited protective activity against HCA-induced cell death.•The anti-epilepsy usage of this TCM was discussed.Five new polyhydroxypregnane glycosides, namely cynanotosides A−E (1–5), together with two known analogues, deacetylmetaplexigenin (6) and cynotophylloside H (7), were isolated from the roots of Cynanchum otophyllum. Their structures were established by spectroscopic methods and acid hydrolysis. The neuroprotective effects of compounds 1–7 against glutamate-, hydrogen peroxide-, and homocysteic acid (HCA)-induced cell death were tested by MTT assay in a hippocampal neuronal cell line HT22. Compounds 1, 2, and 7 exhibited protective activity against HCA-induced cell death in a dose-dependent manner ranging from 1 to 30 μM, which may explain the Traditional Chinese Medicine (TCM) use of this plant for the treatment of epilepsy.Graphical abstractDownload full-size image

Inhibitory effect of ethyl acetate extract of Aristolochia yunnanensis on cardiac fibrosis through extracellular signal-regulated kinases 1/2 and transforming growth factor β/small mother against decapentaplegic signaling pathways

Co-reporter:Weiwei Shao, Dong Li, Jin Peng, Shaorui Chen, ... Xiaoyan Shen

Translational Research (February 2014) Volume 163(Issue 2) pp:160-170

Publication Date(Web):1 February 2014

DOI:10.1016/j.trsl.2013.09.013

Aristolochia yunnanensis, known as Nan Mu Xiang in traditional Chinese medicine, has long been used to treat hypertension and chest pain. In this study, the effect of ethyl acetate extract of Nan Mu Xiang (NMX) on cardiac fibrosis was assessed in vitro by cultured adult rat cardiac fibroblasts with angiotensin II (AngII) stimulation, and in vivo by rats with abdominal aorta constriction (AAC). In cultured adult rat cardiac fibroblasts stimulated by AngII, NMX inhibited cardiac fibroblast proliferation, reduced the expression of fibronectin, α-smooth muscle actin (α-SMA), and transforming growth factor β (TGF-β) in a dose-dependent manner; and suppressed AngII-induced phosphorylation of extracellular signal-regulated kinase (ERK)1/2, C- rapidly accelerated fibrosarcoma (C-Raf), and small mother against decapentaplegic (Smad) 2. Similar results were also observed in AAC rats with intraperitoneal injection of NMX, which not only ameliorated myocardial fibrosis, but also improved cardiac function. The therapeutic effect of NMX on myocardial fibrosis is attributed mainly to the inhibition of ERK and the TGF-β/Smad signaling pathways. NMX may be a promising potential drug candidate for myocardial fibrosis.

Bioactive polyhydroxylated sterols from the marine sponge Haliclona crassiloba

Co-reporter:Zhong-Bin Cheng, Han Xiao, Cheng-Qi Fan, Ya-Nan Lu, Ge Zhang, Sheng Yin

Steroids (20 December 2013) Volume 78(Issue 14) pp:1353-1358

Publication Date(Web):20 December 2013

DOI:10.1016/j.steroids.2013.10.004

•Four new polyhydroxylated sterols were isolated from the sponge Haliclona crassiloba.•This is the first report of a steroid profile for this species.•Compounds 1 and 2 represented rare examples of Δ17(20) steroids.•Structures were established by spectroscopic methods and comparisons with literature values.•Two compounds showed moderate activity against some of the Gram-positive strains.Four new polyhydroxylated sterols, named halicrasterols A–D (1–4), together with six known analogs (5–10) were isolated from the marine sponge Haliclona crassiloba. Compounds 1 and 2 represented rare examples of steroids featuring 17(20)E-double bonds. The structures of 1–10 were elucidated by spectroscopic analysis and comparison with reported data. This is the first report of a steroid profile for this species. The antimicrobial activities of 1–10 were evaluated against a panel of bacterial and fungal strains in vitro, and compounds 4 and 9 showed moderate activity against some of the Gram-positive strains with MICs ranging from 4 to 32 μg/mL.Download full-size image

Inhibition of osteoclastogenesis by 6-[10′(Z)-heptadecenyl] salicylic acid from Syzygium tetragonum Wall via preventing nuclear translocation of NFATc1

Co-reporter:Xin-Wen Zhang, Chun Zhou, Han-Dong Zhu, Weiwei Shao, Yan You, Jin Peng, Sheng Yin, Xiaoyan Shen

Phytomedicine (15 June 2014) Volume 21(Issue 7) pp:960-965

Publication Date(Web):15 June 2014

DOI:10.1016/j.phymed.2014.03.007

Syzygium tetragonum Wall is a Chinese folk medicine for the treatment of rheumatism, joint swelling and pain. By High Content Screening (HCS), 8 compounds (1–8) from Syzygium tetragonum Wall were evaluated for their inhibitory activity on the nuclear translocation of NFATc1 in EGFP-NFATc1 U2OS cells. Among them, 6-[10′(Z)-heptadecenyl] salicylic acid (8) exhibited a significant inhibitory activity. In RAW 264.7 cells, it could dose-dependently prevent nuclear NFATc1 translocation induced by receptor activator of nuclear factor κB ligand (RANKL). The differentiation of osteoclasts from bone marrow derived macrophages (BMMs) was significantly inhibited by 8 in a dose-dependent manner. The mRNA expression of TRAP, CtsK, and MMP9, key enzymes for the bone resorption secreted by osteoclasts, were also significantly down-regulated; and MMP9 activity was also obviously decreased. More importantly, the bone resorption activity of osteoclasts was dose-dependently suppressed by compound 8. Our results suggest that compound 8 can effectively inhibit osteoclastogenesis and bone erosion via preventing NFATc1 nuclear translocation and might be a promising drug candidate for relevant diseases.Download high-res image (256KB)Download full-size image

Natural diarylfluorene derivatives: isolation, total synthesis, and phosphodiesterase-4 inhibition

Co-reporter:Jun-Sheng Zhang, Xin Liu, Jiang Weng, Yan-Qiong Guo, Qing-Jiang Li, Abrar Ahmed, Gui-Hua Tang and Sheng Yin

Inorganic Chemistry Frontiers 2017 - vol. 4(Issue 2) pp:NaN177-177

Publication Date(Web):2016/11/23

DOI:10.1039/C6QO00623J