Publications by authors named "Shao-Jiang Song"

167 Publications

Structural Revisions of Two Highly Aromatic Naphthoquinone-Derived Dimers Based on NMR Analysis, Computer-Assisted Structure Elucidation Methods, and Computations.

Org Lett 2021 Sep 26;23(18):7231-7235. Epub 2021 Aug 26.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China.

Eleucanainones A and B are two structurally complex naphthoquinone-derived dimers whose structure identification is difficult. Large yellow fragments of the preliminary CASE (computer-assisted structure elucidation) analysis revealed that the original structures might be questionable. Structural revisions of the two compounds were proposed on the basis of NMR analysis, CASE methods, conformation analysis, and DFT (density functional theory) NMR calculations with a custom DP4+ analysis. In addition, a polyketide-folded biosynthetic pathway of the two revised structures was proposed.
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http://dx.doi.org/10.1021/acs.orglett.1c02626DOI Listing
September 2021

A comprehensive review: Biological activity, modification and synthetic methodologies of prenylated flavonoids.

Phytochemistry 2021 Nov 14;191:112895. Epub 2021 Aug 14.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address:

Prenylated flavonoids, a unique class of flavonoids which combine a flavonoid skeleton and a lipophilic prenyl side-chain, possess great potential biological activities including cytotoxicity, anti-inflammation, anti-Alzheimer, anti-microbial, anti-oxidant, anti-diabetes, estrogenic, vasorelaxant and enzyme inhibition. Recently, prenylated flavonoids have become an indispensable anchor for the development of new therapeutic agents, and have received increasing from medicinal chemists. The prenylated flavonoids have been outstanding developed through isolation, semi or fully synthesis in a very short period of time, which proves the great value in medicinal chemistry researches. In this review, research progress of prenylated flavonoids including natural prenylated flavonoids, structural modification, synthetic methodologies and pharmacological activities was summarized comprehensively. Furthermore, the structure-activity relationships (SARs) of prenylated flavonoids were summarized which provided a basis for the selective design and optimization of multifunctional prenylated flavonoid derivatives for the treatment of multi-factorial diseases in clinic.
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http://dx.doi.org/10.1016/j.phytochem.2021.112895DOI Listing
November 2021

Identification of natural compounds extracted from crude drugs as novel inhibitors of hepatitis C virus.

Biochem Biophys Res Commun 2021 Aug 12;567:1-8. Epub 2021 Jun 12.

Department of Virology II, National Institute of Infectious Diseases, 162-8640, Tokyo, Japan. Electronic address:

Natural product-derived crude drugs are expected to yield an abundance of new drugs to treat infectious diseases. Hepatitis C virus (HCV) is an oncogenic virus that significantly impacts public health. In this study, we sought to identify anti-HCV compounds in extracts of natural products. A total of 110 natural compounds extracted from several herbal medicine plants were examined for antiviral activity against HCV. Using a Huh7-mCherry-NLS-IPS reporter system for HCV infection, we first performed a rapid screening for anti-HCV compounds extracted from crude drugs. The compounds threo-2,3-bis(4-hydroxy-3-methoxyphenyl)-3-butoxypropan-1-ol (#106) and medioresinol (#110), which were extracted from Crataegus cuneate, exhibited anti-HCV activity and significantly inhibited HCV production in a dose-dependent manner. Analyses using HCV pseudoparticle and subgenomic replicon systems indicated that compounds #106 and #110 specifically inhibit HCV RNA replication but not viral entry or translation. Interestingly, compound #106 also inhibited the replication and production of hepatitis A virus. Our findings suggest that C. cuneate is a new source for novel anti-hepatitis virus drug development.
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http://dx.doi.org/10.1016/j.bbrc.2021.06.022DOI Listing
August 2021

Quassinoids: Phytochemistry and antitumor prospect.

Phytochemistry 2021 Jul 19;187:112769. Epub 2021 Apr 19.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Quassinoids, originating from the oxidative degradation of tetracyclic tirucallane triterpene, are a diverse class of secondary metabolites identifying from nature mostly in Simaroubaceae family. The crucial pharmacological activities and structural complexity of quassinoids have long fascinated scientists due to their medicinal uses, infamous toxicity, and unique biosynthesis. In the past few decades, 482 quassinoids, assigned to 6 skeletons, have been isolated and identified from plants. The names, classes, molecular formula, and plant sources of these secondary metabolites are collated here. This review will be a detailed update of the naturally occurring quassinoids reported from the plant kingdom, providing an in-depth discussion of their diversity, antitumor activities, structure-activity relationship.
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http://dx.doi.org/10.1016/j.phytochem.2021.112769DOI Listing
July 2021

Flavonoid-triazolyl hybrids as potential anti-hepatitis C virus agents: Synthesis and biological evaluation.

Eur J Med Chem 2021 Jun 31;218:113395. Epub 2021 Mar 31.

Key Laboratory of Computational Chemistry Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China. Electronic address:

A series of flavonoid-triazolyl hybrids were synthesized and evaluated as novel inhibitors of hepatitis C virus (HCV). The results of anti-HCV activity assays showed that most of the synthesized derivatives at a concentration of 100 μg/mL inhibited the generation of progeny virus. Among these derivatives, 10m and 10r exhibited the most potent anti-HCV activity and inhibited the production of HCV in a dose-dependent manner. Interestingly, 10m and 10r had no significant inhibitory effect on viral translation or replication. Additional action mechanism studies revealed that the most potent compounds, 10m and 10r, significantly inhibited viral entry to 34.0% and 52.0%, respectively, at 10 μM. These results suggest further effective application of 10m and 10r as potential HCV preventive agents.
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http://dx.doi.org/10.1016/j.ejmech.2021.113395DOI Listing
June 2021

Daphnegiravone D from Daphne giraldii induces cell death by targeting ATR in Hep3B cells.

Bioorg Chem 2021 05 4;110:104802. Epub 2021 Mar 4.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Ataxia telangiectasia and Rad3-related protein (ATR) plays a crucial role in cancer and has become a promising target for cancer therapy. Daphnegiravone D (DGD), which could induce apoptosis and oxidative stress in hepatocellular carcinoma (HCC) cells, but the detailed target protein was still unclear. The study provided that the possible target of DGD against HCC cells was determined by isobaric labels for relative and absolute quantification (iTRAQ) assay. In all changed proteins the fold change of ATR was particularly significant. The results from GO, KEGG and PPI analysis showed that DNA damage, cell cycle, apoptosis, DNA repair related pathways changed and ATR was exactly related to them. Moreover, the mRNA and protein of ATR were both decreased in a concentration-dependent manner, and the results of molecular docking also verified the binding. Additionally, cellular thermal shift assay (CETSA) suggested that DGD could directly target at ATR protein. Furthermore, the knockdown of ATR could increase apoptosis and reactive oxygen species (ROS) which induced by DGD. Since ATR inhibitors were generally used in combination with chemotherapy drugs (especially DNA damage drugs) in clinical trials, we investigated the combined application of DGD and oxaliplatin. The results showed that DGD combined with OXA also increased the apoptosis and ROS production of Hep3B cells over either drug alone. Taken together, this study revealed that DGD targeting ATR could be a promising therapeutic strategy for the treatment of liver cancer.
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http://dx.doi.org/10.1016/j.bioorg.2021.104802DOI Listing
May 2021

Structure elucidation and absolute configuration determination of C, C and C tirucallane triterpenoids from the leaves of Picrasma quassioides (D. Don) Benn.

Phytochemistry 2021 Apr 4;184:112675. Epub 2021 Feb 4.

Key Laboratory of Computational Chemistry Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address:

Seven undescribed tirucallane-type triterpenoids, kumunorquassins A‒E and kumuquassins K and L, along with nine known analogues, have been isolated from the leaves of Picrasma quassioides (D. Don) Benn. Their structures and absolute configurations were elucidated based on comprehensive spectroscopic analyses, single-crystal X-ray diffraction analysis and electronic circular dichroism (ECD). The absolute configuration of cornusalterin J was unequivocally determined by X-ray diffraction based on its p-bromobenzoate derivative. A brief approach was presented in our study, which could rapidly and conveniently determine the relative and absolute configurations of OCH-23 of kumuquassin L and cornusalterins J, H and G depending on the chemical shift differences (Δδ) of C-24 and C-25 and the chemical shifts of C-23, H-23 and H-24. In addition, the cytotoxicities of these compounds against two human tumour cell lines (HepG2 and Hep3B) were evaluated.
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http://dx.doi.org/10.1016/j.phytochem.2021.112675DOI Listing
April 2021

Rapid Approaches for Assignment of the Relative Configuration in 1-Oxygenated 1,2-Diarylpropan-3-ols by H NMR Spectroscopy.

J Nat Prod 2021 01 8;84(1):20-25. Epub 2021 Jan 8.

School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.

The structural elucidation of chiral molecules with more than one stereocenter is usually a tricky problem. In this paper, efficient H NMR spectroscopic approaches for assigning the and configurations of 1-oxygenated 1,2-diarylpropan-3-ols were developed. By analysis of the chemical shift differences of diastereotopic methylene H-3 (Δδ) in CDCl or the chemical shift differences of H-1 and H-2 (Δδ) in methanol-, deuterated dimethyl sulfoxide, and acetone-, the configurations of 1-oxygenated 1,2-diarylpropan-3-ols can be rapidly and conveniently determined.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00828DOI Listing
January 2021

Guaiane-type sesquiterpenoids from the roots of Stellera chamaejasme L. and their neuroprotective activities.

Phytochemistry 2021 Mar 4;183:112628. Epub 2021 Jan 4.

Key Laboratory of Computational Chemistry Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address:

Nine undescribed guaiane-type sesquiterpenoids stelleraterpenoids A‒I, along with seven reported congeners, were isolated and identified from the 70% EtOH extract of the roots of Stellera chamaejasme L. Their chemical structures were elucidated on the basis of various spectral data. The relative configurations were determined by their NOESY spectra and comparison between their experimental and calculated NMR data. The absolute configurations were established by the comparison between the experimental and calculated ECD spectra and further by X-ray single-crystal diffraction analysis. The neuroprotective effects of these compounds on the HO-induced damage in human neuroblastoma SH-SY5Y cells were evaluated. Stelleraguaianone B exhibited the better activity with 71.62% cell viability compared to the positive control Trolox (65.05%) at 12.5 μM, which might be achieved by inhibiting the apoptosis of SH-SY5Y cells based on an annexin V-FITC/PI staining experiment.
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http://dx.doi.org/10.1016/j.phytochem.2020.112628DOI Listing
March 2021

Three new sesquineolignans from the fruits of .

J Asian Nat Prod Res 2020 Dec 17:1-6. Epub 2020 Dec 17.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.

Chemical investigations of the 75% EtOH extract from the fruits of led to the isolation of three undescribed naturally occurring sesquineolignans with two 8--4'-type neolignan moieties, cratapinnatifidas A-C (-). Their chemical structures were elucidated by the comprehensive spectroscopic analyses (HRESIMS, 1D and 2D-NMR). In the bioactivity assay, their cytotoxic activities against two human hepatoma cell lines (HepG2 and Hep3B) were evaluated and no significant activity was seen with IC values ranging from 12.5 to 50.0 μM.
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http://dx.doi.org/10.1080/10286020.2020.1853707DOI Listing
December 2020

Vibsane-type diterpenoids from Viburnum odoratissimum and their cytotoxic activities.

Bioorg Chem 2021 01 24;106:104498. Epub 2020 Nov 24.

Key Laboratory of Computational Chemistry Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address:

Seven new diterpenoids (1-7), including five 7-membered ring vibsane-type diterpenoids, vibsanolide A-E (1-5) and a pair of epimers of 14,15,16,17-tetranorvibsane-type diterpenoids possessing bicyclo[4.2.1]nonane moiety, vibsanolide F-G (6-7), together with twelve known analogues (8-19) were isolated from the crude extracts of the leaves of Viburnum odoratissimum using Small Molecule Accurate Recognition Technology (SMART). These structures including absolute configurations were elucidated by means of comprehensive analyses of spectroscopic data, as well as comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. These compounds were evaluated for their cytotoxic activities against A549 and HepG2 cells by MTT assay. The results showed that compound 2 exhibited potent cytotoxic activity against A549 cells with IC value of 1.11 μM. Further staining experiments indicated that 2 could promote apoptosis induction, enhance reactive oxygen species (ROS) level and attenuate mitochondrial membrane potential (MMP) in A549 cells. Taken together, these findings provided new insights into understanding the cytotoxic activity of vibsane-type diterpenoids and it is meaningful to further investigate the application potential of V. odoratissimum.
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http://dx.doi.org/10.1016/j.bioorg.2020.104498DOI Listing
January 2021

Modified lanostane-type triterpenoids with neuroprotective effects from the fungus Inonotus obliquus.

Bioorg Chem 2020 12 28;105:104438. Epub 2020 Oct 28.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.

Six undescribed lanostane triterpenoids (1-6), together with three known compounds (7-9) were isolated from Inonotus obliquus. Compounds 3-5 are the rare natural compounds featuring a 4,5-seco-lanostane core with a 5,7,9-trien-21,24-cyclopentane moiety. The structure elucidation of the compounds was conducted by spectroscopic techniques and the ECD method. The absolute configuration of compound 1 was confirmed by single-crystal X-ray diffraction analysis. All isolated compounds were assayed for their neuroprotective activity against HO-induced cell injury using human neuroblastoma SH-SY5Y cells. Compound 9 exhibited the most potent neuroprotective activity and the flow cytometry analysis indicated that 9 could protect SH-SY5Y cells from oxidative damage by inhibiting cell apoptosis.
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http://dx.doi.org/10.1016/j.bioorg.2020.104438DOI Listing
December 2020

Targeted isolation of cytotoxic germacranolide sesquiterpenes from Elephantopus scaber L. using small molecule accurate recognition technology.

Bioorg Chem 2020 11 24;104:104314. Epub 2020 Sep 24.

Key Laboratory of Computational Chemistry Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address:

Small molecule accurate recognition technology (SMART) is an emerging method for the rapid structural prediction of major constituents from crude extracts and fractions. In the present study, a targeted isolation of an Elephantopus scaber extract by SMART resulted in the obtention of 15 new (1-15) and five known germacranolide sesquiterpenes (16-20). Their structures were assigned by extensively analyzing HRESIMS, NMR, X-ray crystallographic analyses, modified Mosher's method results, and quantum chemical calculate electronic circular dichroism (ECD) spectra. All germacranolide sesquiterpenes were screened to determine their inhibitory effects with two hepatoma cell lines (HepG2 and Hep3B), and compounds 14, 16, 18, 19 and 20 showed significant cytotoxic activities against the HepG2 (IC, 3.3-9.9 μM) and Hep3B (IC, 4.5-8.6 μM) cell lines. Further study suggested that 18 can induce the apoptosis of hepatoma cells via mitochondrial dysfunction.
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http://dx.doi.org/10.1016/j.bioorg.2020.104314DOI Listing
November 2020

Enantiomeric 8-O-4'-type neolignans from Crataegus pinnatifida exhibit cytotoxic effect via apoptosis and autophagy in Hep3B cells.

Bioorg Chem 2020 11 2;104:104267. Epub 2020 Sep 2.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address:

Crataegus pinnatifida has been famous for its nutritional purpose. However, systematic investigation on the bioactive constituents is still lacking, although this fruit has been reported for its cytotoxic effect before. In this study, two pairs of new lignan enantiomers (1a/1b, 2a/2b), which isolated using chiral chromatographic column from the fruits of C. pinnatifida were studied. The absolute configurations of enantiomers were determined by comparison between the experimental electronic circular dichroism (ECD) and calculated ECD spectra. Among them, 1a/1b exhibited a better cytotoxic effect in hepatocellular carcinoma Hep3B cells with an IC value of 34.97 ± 2.74 and 17.42 ± 0.71 μM, respectively. In addition, 1b induced much more apoptotic, autophagic cells than 1a in Hep3B cells. Furthermore, the underlying mechanism was demonstrated that p38 activation could promote 1b-induced apoptosis and autophagy. Moreover, 1b-induced apoptosis was significantly decreased in the presence of autophagic inhibitor Bafilomycin A1 (Baf A1), suggesting that the induction of autophagy enhanced apoptotic cell death in 1b-treated cells. In general, these findings provide a valuable basis for further understanding the effect of 8-O-4' lignans in C. pinnatifida on cytotoxic effect.
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http://dx.doi.org/10.1016/j.bioorg.2020.104267DOI Listing
November 2020

Sesquiterpenes from Echinacea purpurea and their anti-inflammatory activities.

Phytochemistry 2020 Nov 9;179:112503. Epub 2020 Sep 9.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research and Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address:

Six unreported sesquiterpenes, purpureaterpenes A‒F, together with six known sesquiterpenes, were isolated and identified from the aerial part of Echinacea purpurea. Their chemical structures were established by detailed analyses of 1D and 2D NMR data. The relative configurations were assigned on the basis of their NOESY spectra and the calculated C NMR spectra. Their absolute configurations were determined by X-ray crystallographic analyses and optical rotation calculations. All the isolated compounds were tested for their anti-inflammatory effects against NO production in LPS-induced RAW246.7 macrophages. Among these compounds, purpureaterpene E was the most active (IC value 13.27 μM), even better than the positive control, minocycline (IC value 34.81 μM). Further investigation found that purpureaterpene E might exert anti-inflammatory property via the NF-κB signaling pathway.
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http://dx.doi.org/10.1016/j.phytochem.2020.112503DOI Listing
November 2020

Discovery of dihydro-β-agarofurans from Tripterygium wilfordii with their HO-induced SH-SY5Y cell protective effects.

Bioorg Chem 2020 11 1;104:104247. Epub 2020 Sep 1.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address:

Chemical investigations of the 75% EtOH extract of the leaves of Tripterygium wilfordii obtained five undescribed naturally occurring sesquiterpenes with dihydro-β-agarofuran skeleton, tripteresters A-E (1-5), along with eight known analogues (6-13). Their chemical structures were elucidated by a combination of spectroscopic the comprehensive spectroscopic analyses, electronic circular dichroism (ECD) exciton chirality, and quantum chemical calculations ECD. In the bioactivity assay, their neuroprotective properties against hydrogen peroxide (HO)-induced oxidative damage in human neuroblastoma SH-SY5Y cells were investigated, and compounds 4, 8, and 12 revealed moderate protective activity at a concentration of 12.5 µM.
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http://dx.doi.org/10.1016/j.bioorg.2020.104247DOI Listing
November 2020

Structure elucidation of a new terpenylated coumarin with the combination of CASE algorithms and DFT/NMR approach.

J Asian Nat Prod Res 2020 Aug 21:1-10. Epub 2020 Aug 21.

School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.

One new terpenylated coumarin ailanthuscoumarin was isolated from the root barks of (Mill.) Swingle. The high oxidation of the compound led to the difficulty of structure elucidation by 2D-NMR spectra. Its structure was determined with the aid of computer-assisted structure elucidation (CASE) expert systems and Gauge-independent atomic orbital (GIAO) NMR calculations. The absolute configuration of ailanthuscoumarin was determined by the comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. The anti-hepatoma activity of ailanthuscoumarin against two human hepatoma cells (Hep3B, HepG2) was also reported.[Figure: see text].
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http://dx.doi.org/10.1080/10286020.2020.1804377DOI Listing
August 2020

Germacranolides from Elephantopus scaber L. and their cytotoxic activities.

Phytochemistry 2020 Oct 5;178:112479. Epub 2020 Aug 5.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China. Electronic address:

Seven undescribed germacranolides, named as scabertopinolide A-G were obtained from whole herbs of Elephantopus scaber L. The determination of their structures was conducted via comprehensive spectroscopic analyses combined with experimental electronic circular dichroism (ECD) spectroscopic data and quantum mechanical ECD calculations. The absolute configuration of scabertopinolide A was determined by X-ray crystallography data analysis. The cytotoxicity of all compounds was evaluated against three human cancer cell lines HepG2, Hep3B (human hepatocellular carcinoma cell lines), and MCF-7 (human breast adenocarcinoma cell line). Scabertopinolide G exhibited the most significant cytotoxic activities against the three cancer cell lines with IC values between 7.0 and 10.3 μM. Furthermore, flow cytometry analysis has suggested that scabertopinolide G may cause death of cancer cells through apoptosis induction.
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http://dx.doi.org/10.1016/j.phytochem.2020.112479DOI Listing
October 2020

Terpenoids from stigma maydis (Zea mays L.) alleviate hydrogen peroxide-induced SH-SY5Y cell injury by activating Nrf2.

Bioorg Chem 2020 09 23;102:104131. Epub 2020 Jul 23.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address:

Five terpenoids (1-5), including three new ent-kaurane diterpenoids (1-3), one new ent-rosane type diterpenoid (4) and one known triterpenoid (5), were isolated from stigma maydis (Zea mays L.). The structures of the compounds were elucidated by comprehensive spectroscopic analyses. The relative configurations of stigmanes A-D (1-4) were determined by NOESY experiments. In addition, the relative configuration of stigmane D (4) was further established by NMR calculations. The absolute configurations of these compounds were identified by a comparison of experimental and calculated specific rotations. The neuroprotective effects of these compounds against HO-induced injury in human neuroblastoma SH-SY5Y cells were evaluated, and the results showed that among the compounds, 2 exhibited the most significant neuroprotection. Further study demonstrated that 2 could activate nuclear factor E2-related factor (Nrf2), downregulate apoptosis and reactive oxygen species (ROS) generation, and increase antioxidant enzyme activities in SH-SY5Y cells. However, the neuroprotective effect was reversed when Nrf2 was silenced. In conclusion, this study suggested that terpenoids from stigma maydis exerted neuroprotective effects through Nrf2 activation.
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http://dx.doi.org/10.1016/j.bioorg.2020.104131DOI Listing
September 2020

Lignans and neolignans with isovaleroyloxy moiety from Solanum lyratum Thunb.: Chiral resolution, configurational assignment and neuroprotective effects.

Phytochemistry 2020 Oct 20;178:112461. Epub 2020 Jul 20.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.

Eight pairs of enantiomeric lignans and neolignans including thirteen undescribed compounds, along with an undescribed meso compound, were isolated from the herbs of Solanum lyratum Thunb.(Solanaceae). Their structures and relative configurations were determined by extensive spectroscopic analyses of HRESIMS and nuclear magnetic resonance. The absolute configurations of the pure isomers were established based on the cooperative comparison between the experimental and calculated electronic circular dichroism (ECD) and optical rotation (OR). It is interesting that we obtained several naturally occurring stereoisomers with the identical gross structure possessing several stereogenic carbons from S. lyratum. Additionally, all isolates were assessed for neuroprotective effects toward human neuroblastoma SH-SY5Y cells injury induced by HO.
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http://dx.doi.org/10.1016/j.phytochem.2020.112461DOI Listing
October 2020

A new dilignan from the twigs and leaves of .

J Asian Nat Prod Res 2021 Jun 9;23(6):609-614. Epub 2020 Jul 9.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.

Previous work has shown that the lignans from the twigs and leaves of (Jack) I.C.N. possess anti--amyloid aggregation activity. Here we report a new dilignan, archidendronin A (), along with one known sesquilignan (). Their structures were determined by extensive spectroscopic methods, including UV, HRESIMS, 1 D and 2 D NMR data. The inhibitory activity on A aggregation was screened by ThT assay with curcumin as the positive control, and compounds and showed inhibition rate of 60.0% and 64.4% at 20 M, respectively.[Formula: see text].
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http://dx.doi.org/10.1080/10286020.2020.1791097DOI Listing
June 2021

Isolation and structure elucidation of anti-tyrosinase compounds from the seeds of .

J Asian Nat Prod Res 2021 Aug 6;23(8):738-744. Epub 2020 Jul 6.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.

Three new compounds, crotalariapallins A-C (), were isolated from the 95% EtOH extract of the seeds of . Their structures were established based on extensive spectroscopic methods, including HRESIMS, UV, 1D and 2D NMR. All compounds were evaluated for their inhibitory activities to tyrosinase. These compounds showed different degrees of inhibitory activities, among them, compound exhibited the strongest inhibition activity (IC = 0.42 mM).
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http://dx.doi.org/10.1080/10286020.2020.1782386DOI Listing
August 2021

Chiral-phase resolution of sesquilignans from raspberries (Rubus idaeus L.) and their neuroprotective effects.

Fitoterapia 2020 Oct 2;146:104655. Epub 2020 Jun 2.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address:

Two pairs of diastereoisomers (1/2 and 3/4) were isolated from the fruits of Rubus idaeus L. (Rosaceae). Their structures were elucidated on the basis of extensive spectroscopic analyses. Then chiral-phase HPLC resolution gave 1a/1b-4a/4b. Their absolute configurations were determined by comparison of the experimental ECD with the calculated data. Moreover, all isolated compounds were investigated for the neuroprotective effects against HO-induced neurotoxicity in human neuroblastoma SH-SY5Y cells, and 2a (66.04%) exhibited moderate neuroprotective effects, better than trolox (60.54%) at the concentration of 25 μM.
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http://dx.doi.org/10.1016/j.fitote.2020.104655DOI Listing
October 2020

Phenolics from Archidendron clypearia (Jack) I.C.Nielsen protect SH-SY5Y cells against HO-induced oxidative stress.

Phytochemistry 2020 Aug 20;176:112414. Epub 2020 May 20.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, School of Traditional Chinese Materia Medica, Liaoning province, People's Republic of China. Electronic address:

Five undescribed phenolics named pithecellobiumin C-G, along with thirteen known ones were isolated from the twigs and leaves of Archidendron clypearia (Jack) I.C.Nielsen. Their structures were elucidated based on comprehensive spectroscopic analyses, combined with computer-assisted structure elucidation software (ACD/Structure Elucidator) and gauge-independent atomic orbitals (GIAO) NMR chemical shift calculations. The absolute configurations were determined by comparison of experimental and calculated specific rotation and ECD curves. These compounds were tested for their neuroprotective activities against HO-induced injury in human neuroblastoma SH-SY5Y cells by MTT assay. Pithecellobiumin C-E exhibited noticeable neuroprotective effect. Further pharmacological study demonstrated that they could prevent cell death through inhibiting the apoptosis induction. Flow cytometry assays also proved that these compounds could attenuate reactive oxygen species (ROS) level and mitochondrial dysfunction in SH-SY5Y cells.
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http://dx.doi.org/10.1016/j.phytochem.2020.112414DOI Listing
August 2020

Semi-synthesis and biological evaluation of flavone hybrids as multifunctional agents for the potential treatment of Alzheimer's disease.

Bioorg Chem 2020 07 12;100:103917. Epub 2020 May 12.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address:

7-O-galloyltricetiflavan (GTF), a natural flavonoid, is known to exert anti-oxidation and neuroprotective activity, which are related to the prevention of Alzheimer's disease (AD). In this study, three series of GTF hybrids have been designed, synthesized and evaluated as multifunctional agents for treatment AD. The biological assays indicated that most of them showed strong inhibitory effect on self-induced β-amyloid (Aβ) aggregation, and a significant ability to inhibit ChEs. Among them, compound A15 exhibited best inhibition of Aβ aggregation (78.81% at 20 μM), potent AChE inhibitory potencies (IC, 0.56 μM), and compound C4 presented the highest ability to inhibit BuChE (IC, 5.77 μM). Furthermore, kinetic, molecular modeling and molecular dynamics studies revealed that A15 and C4 could interact with the catalytic active site of AChE and BuChE, respectively. In addition, compounds A15 and C4 could cross the blood-brain barrier in vitro. More importantly, A15 and C4 also showed excellent neuroprotective activities against HO-induced human neuroblastoma SH-SY5Y cells damage and nearly no toxicity on SH-SY5Y cells. All of these outstanding in vitro results indicated A15 and C4 as the leading structure worthy of further investigation.
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http://dx.doi.org/10.1016/j.bioorg.2020.103917DOI Listing
July 2020

Highly modified steroids from Inonotus obliquus.

Org Biomol Chem 2020 05;18(20):3908-3916

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.

Six undescribed steroids were isolated from the fungus Inonotus obliquus. Notably, compounds 1 and 2 represented the first example of 8,14-seco-4-methylpregnane. By spectroscopic data analyses, quantum chemical calculations and DP4+ probability analysis, their structures were unambiguously determined. The absolute configurations of the compounds 1-6 were defined by comparison of their experimental and calculated electronic circular dichroism (ECD) spectra data. The structure of compound 1 was also confirmed by single-crystal X-ray diffraction. All isolated steroids were evaluated for their neuroprotective activities against H2O2-induced cell injury in human neuroblastoma SH-SY5Y cells, among which compound 2 showed moderate activity at 12.5 μM.
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http://dx.doi.org/10.1039/d0ob00474jDOI Listing
May 2020

Elephantopinolide A-P, germacrane-type sesquiterpene lactones from Elephantopus scaber induce apoptosis, autophagy and G2/M phase arrest in hepatocellular carcinoma cells.

Eur J Med Chem 2020 Jul 25;198:112362. Epub 2020 Apr 25.

Key Laboratory of Computational Chemistry Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China. Electronic address:

Chromatographic purification of Elephantopus scaber led to 16 new germacrane-type sesquiterpene lactones (1-16), named elephantopinolide A-P, along with a known analogue (17). Their structures were confirmed by comprehensive spectroscopic analyses, single-crystal X-ray diffraction, and comparison between the experimental and calculated ECD spectra. Their hepatocellular inhibition activities against Hep3B and HepG2 cells were screened by MTT assay, and the structure-activity relationships were examined. The results revealed that 10 (IC value of 2.83 μM and 1.98 μM) is more potent than sorafenib. The underlying mechanism study demonstrated that 10 could markedly induce apoptosis accompanied by increased ROS production and decreased mitochondrial membrane potential, resulting in the autophagy and G2/M phase cell arrest in Hep3B and HepG2 cells. Furthermore, signal pathways including MAPKs and AKT may play important roles in 10-induced hepatocellular carcinoma cells death.
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http://dx.doi.org/10.1016/j.ejmech.2020.112362DOI Listing
July 2020

Terpenylated coumarins from the root bark of Ailanthus altissima (Mill.) Swingle.

Phytochemistry 2020 Jul 11;175:112361. Epub 2020 Apr 11.

School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.

Seven undescribed terpenylated coumarins, named altissimacoumarin I-O, together with seven known compounds, altissimacoumarin C, altissimacoumarin E, altissimacoumarin G, altissimacoumarin H, puberulin, 7-(3-Methyl-2-butenyloxy)-6-methoxycoumarin and artelin were isolated from the root bark of Ailanthus altissima (Mill.) Swingle. Their structures were elucidated by comprehensive spectra data analysis, NMR calculation, DP4+ analysis and ACD/Structure Elucidator software simulation. The absolute configurations of altissimacoumarins K, L, M and N were determined by modified Mosher's method. All isolates were tested for their cytotoxic effect against two hepatoma carcinoma cell lines (HepG2, Hep3B). Altissimacoumarin C exhibited moderate cytotoxic effect against Hep3B cells, with IC of 45.21 μM.
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http://dx.doi.org/10.1016/j.phytochem.2020.112361DOI Listing
July 2020

Sesquineolignans derivatives with neuroprotective activity from the fruits of Crataegus pinnatifida.

Fitoterapia 2020 Jun 8;143:104591. Epub 2020 Apr 8.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Ten undescribed sesquineolignans (1-10), including four sesqui-norlignans (1-4), were isolated from the fruits of Crataegus pinnatifida. Their structures were determined by comprehensive spectroscopic analyses. All compounds were examined for their neuroprotective activities against HO-induced cell injury in human neuroblastoma SH-SY5Y cells. Among them, 6 and 8 showed comparable protective effect with 79.36% and 80.72% cell viability compared with the positive control Trolox (78.64%) at 25 μM.
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http://dx.doi.org/10.1016/j.fitote.2020.104591DOI Listing
June 2020

Sesquiterpenoids from the roots of Daphne genkwa Siebold et Zucc. With potential anti-inflammatory activity.

Phytochemistry 2020 Jun 23;174:112348. Epub 2020 Mar 23.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, PR China. Electronic address:

Six undescribed sesquiterpenoids, including three acorane-type sesquiterpenoids (daphneaines A-C), three guaiane-type sesquiterpenoids (daphneaines E-G) and three known analogues were isolated from the roots of Daphne genkwa Siebold et Zucc. Their gross structures were elucidated by comprehensive spectroscopic analyses. The relative configurations of daphneaines A-C were determined by NOESY experiments. In addition, the relative configuration of daphneaine G was elucidated by performing a quantum chemical calculation of the NMR chemical shifts coupled with an advanced statistical procedure DP4+. The comparison of experimental and calculated electronic circular dichroism (ECD) data led to the establishment of the absolute configurations of daphneaines A-G. All isolates were tested for their inhibitory activity towards the LPS-induced NO production in RAW 264.7 macrophages, and daphneaine F showed inhibitory effect on NO production with an IC value of 35.68 ± 3.18 μM.
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http://dx.doi.org/10.1016/j.phytochem.2020.112348DOI Listing
June 2020
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