69977-52-2Relevant articles and documents
Evaluation of the antidepressant activity, hepatotoxicity and blood brain barrier permeability of methyl genipin
Che, Xin,Wang, Meiyu,Wang, Tian,Fan, Huaying,Yang, Mingyan,Wang, Wenyan,Xu, Hui
, (2016)
Geniposide (GE) is the main bioactive component of Gardeniae Fructus. The hepatotoxicity of geniposide limited clinical application. In order to get a new geniposide derivative that has less hepatotoxicity and still possesses the antidepressant activity, a new C-1 hydroxyl methylation derivative named methyl genipin (MG) was synthesized from geniposide. In the present study, we demonstrated that MG did not increase the liver index, alanine aminotransferase (ALT) and aspirate aminotransferase (AST). Histopathological examination suggested that no toxic damages were observed in rats treated orally with MG (0.72 mmol/kg). More importantly, a 7-day treatment with MG at 0.13, 0.26, and 0.52 mmol/kg/day could reduce the duration of immobility. It showed that the antidepressant-like effects of MG were similar to GE in the tail suspension test and the forced swim test. Furthermore, we found MG could be detected in the brain homogenate of mice treated orally with MG 0.52 mmol/kg/day for 1 day by HPLC. The area under the curve (AUC) of MG in the brain homogenate was enhanced to 21.7 times that of GE. The brain amount and distribution speed of MG were improved significantly after oral administration. This study demonstrated that MG possessed the antidepressant effects and could cross the blood-brain barrier, but had less hepatotoxicity.
1-O-alkyl genipin and preparation method and application thereof
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Paragraph 0136; 0146-0151, (2022/01/04)
The invention belongs to the technical field of genipin derivative synthesis, and particularly relates to 1-O-alkyl genipin and a preparation method and application thereof. The invention provides the preparation method of 1-O-alkyl genipin, the preparation method comprises the following steps: mixing a raw material A, low-carbon alcohol, a Lewis acid catalyst and a polar organic solvent, and carrying out an alkoxylation reaction to obtain 1-O-alkyl genipin, the raw material A comprising genipin and/or 10-O-Piv-1-O-NHCCl3 genipin. In the 1-O-alkyl genipin obtained by the preparation method, the conformation of the 1R-O-alkyl genipin is dominant, and the neuroprotective activity is higher.
Novel genipin derivatives and preparation method and application thereof
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Paragraph 0263-0265; 0266-0268, (2021/06/23)
The invention provides novel genipin derivatives and a preparation method thereof. The novel genipin derivatives comprise geniposide derivatives and genipin derivatives. The invention belongs to the field of pharmaceutical chemistry. The geniposide derivative has a structure shown as a formula (I).
Synthesis and biological evaluation of geniposide derivatives as potent and selective PTPlB inhibitors
Lei, Shuwen,Zhang, Dongdong,Qi, Yunyue,Chowdhury, Sharmin Reza,Sun, Ran,Wang, Juntao,Du, Yi,Fu, Lei,Jiang, Faqin
, (2020/08/03)
Herein a series of Geniposide derivatives were designed, synthesized and evaluated as protein tyrosine phosphatase 1B (PTPlB) inhibitors. Most of these compounds exhibited potent in vitro PTP1B inhibitory activities, the representative 7a and 17f were found to be the most potent inhibitors against the enzyme with IC50 values of 0.35 and 0.41 μM, respectively. More importantly, they showcased 4 to10-fold selectivity over SHP2 and 3-fold over TCPTP. Further biological activity studies revealed that compounds 7a, 17b and 17f could effectively enhance insulin-stimulated glucose uptake with no significant cytotoxicity. Subsequent molecular docking and structural activity relationship analyses demonstrated that the glucose scaffold, benzylated glycosyl groups, and arylethenesulfonic acid ester significantly impact on the activity and selectivity.
Design, synthesis, and evaluation of genipin derivatives for the treatment of Alzheimer's Disease
Huang, Weijun,Wang, Yujun,Li, Jiaming,Zhang, Yanchun,Ma, Xiaodong,Zhu, Panhu,Zhang, Yang
, p. 110 - 122 (2018/12/11)
Twenty-two novel genipin derivatives have been designed, synthesized, and evaluated for their inhibitory activity against acetylcholinesterase (AChE). As a result, compound 13a bearing ligustrazine moiety displayed the most potent AChE inhibitory activity in this series with IC50 value of 218?nm. Besides, MTT assay was performed to investigate the neuroprotection of these compounds against PC12 cells injured by Amyloid β-protein 1–42 (Aβ1–42). Among them, 8a showed higher inhibition rate (%Inhibition?=?22.29) than the positive reference Donepezil (%Inhibition?=?17.65).
Design and synthesis of novel monoterpenoid indole alkaloid-like analogues and their antitumour activities: In vitro
Fang, Jiaqi,Huang, Tao,Xia, Mengyuan,Deng, Lulu,Hao, Xiaojiang,Wang, Yuehu,Mu, Shuzhen
, p. 3026 - 3037 (2018/05/03)
A biomimetic synthetic strategy and combinatorial chemistry were used to synthesize 34 novel monoterpenoid indole alkaloid (MIA) analogues, and their cytotoxic activities against five cancer cell lines (SW-480, A-549, HL-60, SMMC-7721, and MCF-7) were determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Fourteen of these analogues (7, 16-18, and 23-32) showed significantly greater inhibition of tumour cell proliferation than cisplatin. Compounds 17 and 18 showed the highest cytotoxic activity against the HL-60 cell line with IC50 values of 0.90 μM and 0.43 μM, respectively. Compound 18 slightly induced apoptosis and arrested the cell cycle in SW-480, A-549, HL-60, SMMC-7721, and MCF-7 cells. Analysis of the primary structure-activity relationships reveals that the introduction of different substituent groups at the C-3, C-5, and C-6 positions of the indole moiety and the C-10 position of the genipin moiety might have an effect on the antitumour activity of the resulting compounds.
Genipin derivatives and their preparation method and use
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Paragraph 0124-0126, (2018/03/01)
The invention provides genipin derivatives and their preparation method and use and specifically discloses genipin derivatives having novel structures shown in the formula I. The groups are defined in the specification. The invention also discloses a preparation method of the compounds and use of the compounds as protein tyrosine phosphatase 1B (PTP1B) inhibitors. The compounds produce good anti-diabetic effects and have an application value in preparation of drugs for treating type II diabetes.
Design, synthesis and biological evaluation of valepotriate derivatives as novel antitumor agents
Zhang, Bo,Guo, Ruiying,Hu, Yongzhou,Dong, Xiaowu,Lin, Nengming,Dai, Xiaoyang,Wu, Honghai,Ma, Shenglin,Yang, Bo
, p. 31899 - 31906 (2017/07/10)
Natural products remain the largest resources of lead compounds that can be used to develop novel anticancer drug candidates. Based on deacetylisovaltratum, a natural product with promising anticancer activity, herein we designed and synthesized of a series of valepotriate derivatives with a novel skeleton from commercially available genipin. In addition, a structure-activity relationship study demonstrated the importance of an epoxy group on the C1-position and the preferable size of the sidechain ((5-methylhexanoyl)oxy) on the C-7 position of valepotriates for their cytotoxic activities. The most potent compound 1e showed moderate to good IC50 values against various cancer cells, ranging from 10.7 to 50.2 μM, which are comparable to that of deacetylisovaltratum. Additionally, we demonstrate that mitochondrion-mediated apoptosis would be its mechanism of action, thus enlightening the further development of novel valepotriate derivatives.
Inhibiting cyclooxygenase - 2 of the compound and its preparation method and application (by machine translation)
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Paragraph 0073; 0074; 0075; 0076, (2017/08/25)
Inhibiting cyclooxygenase - 2 compound, its structural formula is as follows: through the toxicology, the pharmacodynamics experiment shows, the invention inhibits the cyclooxygenase - 2 compound to the mouse did not affect the body weight, toxic side effect is smaller, compared with the ASP, inhibiting cyclooxygenase - 2 compound to the mouse gastrointestinal toxic side effect is smaller, shows that its high safety; in addition, the invention inhibits the cyclooxygenase - 2 selective inhibiting compound can be COX - 2 expression, but also anti-inflammatory effect is good, obviously stronger-than-GEP and ASP, has very good application prospect. (by machine translation)
Valerenic acid derivatives, pharmaceutical composition comprising same and anti-tumor application of valerenic acid derivatives
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Paragraph 0042; 0043; 0044, (2016/12/16)
The invention provides valerenic acid derivatives, pharmaceutical composition comprising the same and an anti-tumor application of the valerenic acid derivatives. Simple and available genipin as a natural product is taken as a raw material, structural constraint of a conventional natural extract is changed with a semisynthetic method, a series of valerenic acid derivatives with anti-tumor activity are designed and synthesized, the valerenic acid derivatives show better anti-tumor activity in in-vitro experiments, and the compounds can be applied to anti-tumor drug study through further experiments.
