ACS Sustainable Chemistry & Engineering
·
2022
·
IF 9.224
Zheng-Meng Jiang,Fang-Fang Wang,Jie Liu,Tian-Qing Huang,Hu Zhang,E-Hu Liu
The conversion of diester-diterpenoid alkaloids (DAs) into monoester-diterpenoid alkaloids (MAs) is an effective method to reduce the toxicity of Aconiti Lateralis Radix Praeparata (Fuzi in Chinese, ALRP), a popular traditional Chinese medicine. In the present study, deep eutectic solvents (DESs) were first utilized to simultaneously detoxify ALRP and extract aconitum alkaloids by gas bath thermostatic oscillator-assisted extraction. The effects of extraction parameters, including the extraction time, water content of DESs, temperature, liquid/solid ratio, and pH, on the extraction of MAs were evaluated by single-factor experiments, and the optimal condition was further optimized using response surface methodology. The results indicated that betaine-urea (Bet-Ure, 1:2 mol/mol) was the most appropriate DES to hydrolyze highly toxic DAs into less toxic MAs and improve the extraction efficiency of aconitum alkaloids in one step. The detoxification mechanism study showed that alkaline DESs had an excellent efficiency for DA hydrolysis and MA extraction, and the MA-extraction efficiency enhanced with the increase in pH. Compared with the conventional extraction, the newly developed detoxification process maximized the hydrolysis of DAs and exhibited a higher MA-extraction efficiency (1.913 mg/g vs 0.155 mg/g). The DES-based method offered an ecofriendly, simple, and feasible detoxication strategy for ensuring the safe and effective use of ALRP.
研究领域:
中药学
·
植物化学
✓ 已验证
产品关联
DOI
高影响因子
CHEMISTRY & BIODIVERSITY
·
2025
·
IF 2.5
Shi-Xing Liu,Qian Wang,Li Jiang,Shang-Gao Liao,Qing-De Long,Xu Zhang,Xue-Long Yan
Phytochemistry investigation of Euphorbia helioscopia led to the isolation of 22 diterpenoids, including five lathyranes, 11 jatrophanes, and six other types. Among them, eupholine A and B ( 1 and 2 ) are a pair of previously undescribed C-6′ lathyrane epimers. The chemical structures of 1–22 were elucidated using spectral data analysis, and the absolute configurations of 1 together with another jatrophane diterpenoid ( 3 ) were determined by X-ray single-crystal diffraction techniques. Besides, the full nuclear magnetic resonance (NMR) assignments of 3 and 4 were first determined by analysis of their two-dimensional NMR data. All the isolates were screened for inhibition activity of fibrinogen on transforming growth factor-β1-stimulated LX-2 cells, and seven compounds (mainly lathyranes and jatrophanes types) showed certain inhibitory effects at 20 µM, being comparable to that of the positive control, silymarin. Notably, compound 14 (jatrophane type) showed significant inhibitory activity that is superior to silymarin. The study suggested that jatrophane diterpenoids and their analogs (lathyrane types) may serve as a potential chemical entity against liver fibrosis. Graphical
研究领域:
植物化学
·
药理学
·
生物医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2020
·
IF 4.192
Gui-Lin Hu,Ya Gao,Xing-Rong Peng,Jun-Hong Liu,Hai-Guo Su,Yan-Jie Huang,Ming-Hua Qiu
Seven new lactam ent-kaurane diterpenoids, cafemides A–G (1–7), were isolated from roasted beans of Coffea arabica. Their structures were elucidated by extensive spectroscopic analysis including 1D, 2D NMR (heteronuclear single quantum correlation (HSQC), heteronuclear multiple bond correlation (HMBC), 1H–1H correlation spectroscopy (COSY), and rotating frame Overhauser effect spectroscopy (ROESY)), high-resolution electrospray ionization mass spectrometry (HRESIMS), and IR spectra. They were divided into subtype I–III according to the structure. Further, with the aid of liquid chromatography–tandem mass spectrometry (LC–MS/MS) based molecular network, seven (8–14) subtype II diterpenoids were successfully identified. In addition, a variety of other subtypes of N-containing diterpenoids have been proven in roasted coffee. Compounds 1, 2, 3, 5, and 7 showed a moderate inhibitory effect on α-glucosidase with an IC50 value of 8.28 ± 0.62 μM, 38.23 ± 8.87 μM, 28.94 ± 1.42 μM, 12.44 ± 1.37 μM, and 22.2 ± 5.34 μM, respectively. To the best of our knowledge, this is the first time that N-containing diterpenoids have been reported in coffee.
研究领域:
植物化学
·
食品科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2018
·
IF 4.946
Xia Wang,QianQian Meng,XingRong Peng,GuiLin Hu,MingHua Qiu
Eight new ent -kaurane diterpene fatty acid esters, namely caffarolides A–H ( 1 – 8 ), were isolated from green beans of Coffea arabica . Their chemical structures were confirmed by extensive spectroscopic analysis including 1D, 2D NMR (HSQC, HMBC, 1 H– 1 H COSY, and ROESY), HRMS, IR and CD spectra and by GC-FID analysis. Interestingly, the diterpene moiety of these new compounds first occurred in genus Coffea . All the isolates were evaluated for platelet aggregation activity in vitro . As the results, caffarolides C, D and F ( 3 , 4 and 6 ) showed induction effect for platelet aggregation and the possible structure-activity relationships have been discussed briefly.
研究领域:
植物化学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Forests
·
2022
·Vol. 13
·期 2
·283
·
IF 3.282
Yini Zhang,Xianyin Ding,Qifu Luan,Jingmin Jiang,Shu Diao
Diterpene resin acids (DRAs) are major components of pine oleoresin that can effectively resist the invasion of insects and pathogenic microorganisms. The subfamily of cytochrome P450s, CYP720B, catalyzes diterpene products into DRAs. Identifying CYP720B subfamily members and revealing the characteristics of tissue-specific expression would help understand diterpene-rich structures and diverse types. Slash pine and loblolly pine are important pines that provide oleoresin products. In this study, we identifiedCYP720Bcandidate genes based on thePinus taedaV2.0 genome and full-length transcriptome of slash pine by PacBio. A total of 17 genes in slash pine and 19 in loblolly pine were identified and classified into four main clades by phylogenetic analysis. An analysis ofcis-acting elements showed thatCYP720Bgenes were closely related to adversity resistance. The gene expression of these candidates in different tissues was quantified by real-time quantitative PCR (RT–qPCR) analysis. Most of the genes showed relatively higher expression levels in roots and stems than in the other tissues, corresponding with the results of DRA component detection by gas chromatography–mass spectrometry (GC–MS), which indicated that stems and roots might be important tissues in oleoresin biosynthesis. These results provide a valuable resource for a better understanding of the biological role of individual CYP720Bs in slash pine and loblolly pine.Keywords:diterpene resin acids;CYP720B;expression patterns;biotic and abiotic stress
研究领域:
植物学
·
分子生物学
✓ 已验证
DOI
高影响因子
PHYTOCHEMISTRY
·
2018
·
IF 3.186
Xing-Long Chen,Fang Liu,Xue-Rong Xiao,Xiu-Wei Yang,Fei Li
Tripterygium hypoglaucum (H. Lév.) Hutch. has been used to remedy rheumatoid arthritis , however, it shows frequent toxicity to the body. In this study, liquid chromatograph-mass spectrometer (LC-MS) was guided to characterize abietanes diterpenoids with anti-inflammatory activity from the stem of T. hypoglaucum . Thirteen undescribed abietanes diterpenoids were isolated and purified, and their chemical structure was identified using various spectroscopic methods . These compounds belonged to abietanes with splitting C ring, abietanes with benzenoid rings, diterpene quinoids , diterpene quinoids with lactone rings, and abietanes with benzenoid and lactone rings, respectively. Lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages was used to evaluate anti-inflammatory activity of the compounds. The results indicated that hypoglicin B-G and hypoglicin J-M exhibited inhibitory activity of NO production with the IC 50 values of 6.01, 25.21, 8.29, 3.63, 0.72, 0.89, 36.91, 0.82, 2.85, 11.92 μM, respectively. Among these compounds, compound hypoglicin L showed high anti-inflammatory activity and low toxicity (SI = 5.02 × 10 4 ). Further QPCR analysis revealed that hypoglicin D and hypoglicin L can inhibit the mRNA expression of iNOS in LPS-stimulated RAW264.7 cells at doses of 12.5 and 3.13 μM, respectively. Taken together, ten anti-inflammatory diterpenoids were found from T. hypoglaucum in this study.
研究领域:
药理学
·
植物化学
✓ 已验证
DOI
PubMed
高影响因子
MEDICINAL CHEMISTRY RESEARCH
·
2020
·Vol. 29
·期 8
·1341-1354
·
IF 1.783
Zhu Shi-ying,Luo Fa-zeng,Sun Ping-Hua
Gibberellic acid (GA 3 ) is a tetracyclic diterpene compound which displays interesting bioactivities. Recently, its potential use for preparing antitumor drug leads has been highlighted, and various modification methods of GA 3 have been reported. Aiming at investigating GA 3 derivatives with potential antitumor activities, ring distortion of GA 3 under different conditions was carried out, and this was followed with amidation or substitution, yielding four series of derivatives. The chemical structure of these compounds were analyzed by 1 H-NMR, 13 C-NMR, HRMS, FTIR and polarimetry, and SXRD was employed to further confirm the spatial configurations of derivatives 3c and 7d . The antitumor activities of three series of derivatives were evaluated by using MTT assay and ELISA. Results shows that, among amide derivatives, compounds with a saturated linear amide showed better activity than those with an aromatic amide. Among ester derivatives, compounds with a meta -substituted benzyl group showed better activities than those with a para -substituted benzyl group. The antitumor activity of ester derivatives might possibly be linked with the inhibition of FGFR 1 activation and KDR activation. Overall, this study discussed how the antitumor activity of GA 3 was formed, thereby assisting the future design of more effective active GA 3 derivatives.
研究领域:
有机化学
·
药理学
·
肿瘤学
✓ 已验证
DOI
高影响因子
JOURNAL OF NATURAL PRODUCTS
·
2025
·
IF 3.6
Mi Zhou,Yanlan Yang,Shoulun He,Qiannan Xu,Chunchun Du,Wenjing Tian,Haifeng Chen
Phosphorylation of checkpoint kinase 1 at Ser-345 (p-CHK1(S345)) mediates the replication stress response in cancer cells, leading to chemotherapy resistance. Therefore, finding inhibitors of p-CHK1(S345) is currently a promising strategy to prevent acquired drug resistance. In this study, 14 ingenane diterpenoids (1–14), involving two undescribed compounds possessing an unprecedented exocyclic double bond Δ6(20), were identified from Euphorbia peplus. The inhibitory effects of the isolated compounds on p-CHK1(S345) and their structure–activity relationship (SAR) were investigated. Compounds 7 and 8 presented the strongest inhibitory effects, abrogated cell cycle arrest, and caused the accumulation of DNA damage, improving the sensitivity of cancer cells to chemotherapeutic drugs. An in vivo assay confirmed the enhancement of 8 on the anticancer effect of topotecan via blocking of p-CHK1(S345). Mechanistically, 8 increased CHK1 ubiquitination to inhibit p-CHK1(S345) via activation of protein kinase C (PKC). PKC activation was first found to enhance CHK1 ubiquitination to block p-CHK1(S345). Above all, this finding not only indicates that compound 8 could be developed as a novel CHK1 inhibitor but also reveals a previously unrecognized role of PKC in regulating cancer chemotherapy sensitivity.
研究领域:
肿瘤学
·
药理学
·
植物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2018
·Vol. 15
·期 11
·e1800386
·
IF 1.617
Qian Wang,Yong-Qi Zhen,Feng Gao,Shuai Huang,Xian-Li Zhou
A new premyrsinane-type diterpenoid, premylanin ( 1 ), and four new lathyrane-type diterpenoids named Euphorbia Factors L 30 –L 33 ( 2 – 5 ) were isolated from the seeds of Euphorbia lathyris , together with thirteen known ones ( 6 – 18 ). Their structures were elucidated through spectroscopic analyses, including IR, UV, HR-ESI-MS, 1D- and 2D-NMR. The cytotoxicities of compounds 1 – 4 and 6 – 18 against HCT116, MCF-7, 786–0, HepG2 cell lines were evaluated, and compound 13 exhibited considerable cytotoxic activities with an IC 50 values of 6.44, 8.43, 15.3, 9.32 μ m , respectively. Graphical
研究领域:
植物化学
·
药理学
·
肿瘤学
✓ 已验证
DOI
高影响因子
METABOLIC ENGINEERING
·
2020
·
IF 7.263
Tianyuan Hu,Jiawei Zhou,Yuru Tong,Ping Su,Xinlin Li,Yuan Liu,Nan Liu,Xiaoyi Wu,Yifeng Zhang,Jiadian Wang,Linhui Gao,Lichan Tu,Yun Lu,Zhouqian Jiang,Yongjin J. Zhou,Wei Gao,Luqi Huang
Miltiradiene is a key intermediate in the biosynthesis of many important natural diterpene compounds with significant pharmacological activity, including triptolide, tanshinones, carnosic acid and carnosol. Sufficient accumulation of miltiradiene is vital for the production of these medicinal compounds. In this study, comprehensive engineering strategies were applied to construct a high-yielding miltiradiene producing yeast strain. First, a chassis strain that can accumulate 2.1 g L -1 geranylgeraniol was constructed. Then, diterpene synthases from various species were evaluated for their ability to produce miltiradiene, and a chimeric miltiradiene synthase, consisting of class II diterpene synthase (di-TPS) Cf TPS1 from Coleus forskohlii ( Plectranthus barbatus ) and class I di-TPS Sm KSL1 from Salvia miltiorrhiza showed the highest efficiency in the conversion of GGPP to miltiradiene in yeast. Moreover, the miltiradiene yield was further improved by protein modification, which resulted in a final yield of 550.7 mg L -1 in shake flasks and 3.5 g L -1 in a 5-L bioreactor . This work offers an efficient and green process for the production of the important intermediate miltiradiene, and lays a foundation for further pathway reconstruction and the biotechnological production of valuable natural diterpenes.
研究领域:
生物工程
·
药学
·
合成生物学
✓ 已验证
DOI
PubMed
高影响因子
NATURAL PRODUCT RESEARCH
·
2014
·
IF 1.225
Mingliang Zhong,Haifeng Wu,Xiaopo Zhang,Guangli Sun,Guibo Sun,Shichun Yu,Xudong Xu
A new abietane diterpene, named as 3β-hydroxy-12-O-β-d-glucopyranosyl-8,11,13-abietatrien-7-one (1), together with four known flavonoids, was isolated from the hot water extract of the aerial parts of Clinopodium chinense. Their structures were determined by analysing the spectroscopic data including 1D, 2D NMR and HR-ESI-MS. Compound 1 tested against HepG-2 and A549 cancer cell lines expressed weak cytotoxicity. Cardioprotective effects of compounds 2–5 against H2O2-induced apoptosis in H9c2 cells were also evaluated; compounds 2 and 3 exhibited moderate cardioprotective effect.
研究领域:
植物化学
·
药理学
·
肿瘤学
·
心血管科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2022
·
IF 4.601
Yang Yu,Changliang Yao,Wenlong Wei,Haojv Li,Yong Huang,Shuai Yao,Hua Qu,Qinhua Chen,Quanxi Mei,Wanying Wu,De-an Guo
The hyphenated technique of offline two-dimensional (2D) chromatography with high resolution mass spectrometry (MS) was an efficient tool for separation and characterization of components in complex systems such as herbal medicines, especially those co-eluting components or isomers. In this study, we constructed the ultra-performance convergence chromatography (UPC 2 ) × reversed phase (RP) chromatographic separation system and developed a mass defect filtering (MDF)-based precursor ion list (PIL) acquisition method to improve the selectivity and sensitivity of this technique, and the systematic characterization of diterpenoid alkaloids in the lateral roots of Aconitum carmichaelii (namely “Fuzi” in Chinese) was used as an example. The constructed offline 2D separation system showed a good orthogonality of 0.77. Besides, the in-house databases for known and predicted C 19 - and C 20 -diterpenoid alkaloids were established by molecular design in Compound Discoverer software for MS data matching and filtering, and two MDF windows were further constructed to screen out more potential diterpenoid alkaloids with novel structures and to obtain the PIL (mass range: even values between 298 and 1020 Da, parent mass width: ±100 mDa) for data acquisition by calculating the m/z values of potential ions using mass range and corresponding mass defect in the MDF windows. In addition, an integrative structure interpretation strategy was developed by integrating elemental composition analysis, ring double bond analysis, neutral loss filtering, diagnostic ion filtering and database matching, etc. As a result, a total of 659 components in the lateral roots of A. carmichaelii were exposed and characterized, including 526 potential new compounds. This strategy showed significant advantages in improving the coverage and selectivity of screening, and could also be applied in systematic characterization of components in other herbal medicines.
研究领域:
中药化学
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）