- Discovery of 4′-O-methylscutellarein as a potent SARS-CoV-2 main protease inhibitor
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The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths and seriously threatened public health and safety. Despite COVID-19 vaccines being readily popularized worldwide, targeted therapeutic agents for the treatment of this disease remain very limited. Here, we studied the inhibitory activity of the scutellarein and its methylated derivatives against SARS-CoV-2 main protease (Mpro) by the fluorescence resonance energy transfer (FRET) assay. Among all the methylated derivatives we studied, 4′-O-methylscutellarein exhibited the most promising enzyme inhibitory activity in vitro, with the half-maximal inhibitory concentration value (IC50) of 0.40 ± 0.03 μM. Additionally, the mechanism of action of the hits was further characterized through enzyme kinetic studies and molecular docking. Overall, our results implied that 4′-O-methylscutellarein could be a primary lead compound with clinical potential for the development of inhibitors against the SARS-CoV-2 Mpro.
- Li, Maotian,Li, Yingxia,Wang, Yujie,Wu, Qianqian,Xiao, Yibei,Yan, Shiqiang
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- Semi-synthesis of a series natural flavonoids and flavonoid glycosides from scutellarin
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Natural flavonoids and flavonoid glycosides exist in many plants and have been demonstrated to possess various clinically relevant properties, isolating large amounts of these compounds that have striking structural similarity from plant sources needs tedious isolation techniques. These processes limited their availability in structural diversity for structure?activity relationship (SAR) studies, and restrict large quantities for, as an example, their mechanistic evaluation of the in vivo activities. In this work, we developed a semi-synthetic strategy from scutellarin for the synthesis of a series of natural flavonoids and flavonoid glycosides. By taking this strategy, eight bioactive flavonoids with striking structural similarities were synthesized efficiently and practically. The sufficient amounts obtained products will greatly facilitate the SAR studies and mechanistic evaluation of the in vivo activities.
- Ding, Ning,Li, Yingxia,Wang, Yujie,Xiao, Qiang,Xie, Mingxian,Yan, Shiqiang
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- Scutellarin amide derivative, and preparation method and application thereof
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The invention discloses a scutellarin amide derivative, and a preparation method and application thereof, and belongs to the field of natural medicines and medicinal chemistry. The scutellarin derivative and the pharmaceutically acceptable salt thereof have structures shown as the following general formula I. The scutellarin derivative is prepared by amidation at a carbohydrate carboxyl site and is applied to preparation of anti-tumor drugs. Good anti-tumor cell proliferation effects are achieved.
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Paragraph 0018; 0029-0031; 0032-0034
(2020/09/16)
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- Furazan NO-donating scutellarin derivative with anti-tumor activity, and preparation method and application thereof
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The invention relates to the field of natural medicine and medicinal chemistry, in particular to a furazan NO-donating scutellarin derivative with anti-tumor activity, and a pharmaceutically acceptable salt thereof. The invention specifically relates to the furazan NO-donating substituted scutellarin derivatives with an aliphatic chain connecting arm on uronic acid base loci, and application for preparing anti-tumor drugs. The structures of the furazan NO-donating scutellarin derivative and the pharmaceutically acceptable salt thereof are shown in the following general formula I, wherein R and R1 are disclosed in claims and specifications. The formula is shown in the specification.
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Paragraph 0023; 0024; 0025; 0026; 0027; 0028
(2017/07/19)
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- Furazan type NO (nitric oxide) donor scutellarin derivative with anti-tumor activity and preparation method and application thereof
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The invention relates to the field of natural medicines and medicine chemistry, in particular to a furazan type NO (nitric oxide) donor scutellarin derivative with anti-tumor activity and a pharmaceutically acceptable salt thereof, and in particular to a furazan type NO donor-substituted scutellarin derivative with a piperazine ringfatty chain link arm on saccharide carboxyl sites and a preparation method and application thereof in preparing anti-tumor medicines. The structures of the furazan type NO donor scutellarin derivative with anti-tumor activity and the pharmaceutically acceptable salt thereof are shown in the formula I, wherein R and n R1 are described in the right claim and instructiondescription. The formula I is shown in the descriptionattached figure.
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Paragraph 0024; 0025; 0026; 0027
(2017/08/31)
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- Nitrate type NO (nitric oxide) donor scutellarin derivative with anti-tumor activity and preparation method and application thereof
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The invention relates to the field of natural medicines and medicine chemistry, in particular to a nitrate type NO (nitric oxide) donor scutellarin derivative with anti-tumor activity and a pharmaceutically acceptable salt thereof, and in particular to a nitrate type NO donor-substituted scutellarin derivative with a fatty chain link arm on saccharide carboxyl sites and a preparation method and application thereof in preparing anti-tumor medicines. The structures of the nitrate type NO donor scutellarin derivative with anti-tumor activity and the pharmaceutically acceptable salt thereof are shown in the formula I, wherein R and n are described in the right claim and descriptioninstruction. The formula I is shown in the descriptionattached figure.
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Paragraph 0023; 0025; 0026; 0028
(2017/08/30)
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- Scutellarin derivatives as apoptosis inducers: Design, synthesis and biological evaluation
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To explore novel antitumor agents with high efficiency and low toxicity, a series of NO-donating scutellarin derivatives (14–17) were synthesized and the antiproliferative activities against MCF-7, HCT-116, PC-3 and HepG2 cancer cell lines were assessed. Among them, compound 14b was the strongest with IC50 values of 2.96?μM, 7.25?μM, 0.09?μM and 0.50?μM, respectively, and displayed low toxicity against normal human liver L-O2 cells with an IC50 of 47.96?μM, showing good selectivity between normal and malignant liver cells. Moreover, NO releasing ability of the derivatives has been studied. Mechanism studies of the most promising compounds 14b and 15a were carried out. The results indicated that 14b and 15a could induce apoptosis, cell cycle arrest at the S phase and led to mitochondrial dysfunction in the HepG2 and PC-3?cell lines, respectively. Furthermore, Human Apoptosis Protein Array kit assay demonstrated that 14b could induce apoptosis through down-regulating the levels of procaspase-3 and inhibiting the expression of survivin, c-IAP1, HSP27, HSP60, HSP70, HO-1/HMOX1/HSP32 and HO-2/HMOX2 in HepG2 cell line. These results guaranteed compound 14b to be a drug candidate against liver cancer for further investigation.
- Han, Tong,Li, Jia,Xue, Jingjing,Li, He,Xu, Fanxing,Cheng, Keguang,Li, Dahong,Li, Zhanlin,Gao, Ming,Hua, Huiming
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supporting information
p. 270 - 281
(2017/05/01)
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