- Synthesis of colletotrichumine A
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A short synthesis of colletotrichumine A, an oxindole-pyrazine alkaloid isolated from the pathogenic fungus Colletotrichum capsici, is described.
- Varnava, Kyriakos G.,Sperry, Jonathan
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- Discovery of potential anticancer multi-targeted ligustrazine based cyclohexanone and oxime analogs overcoming the cancer multidrug resistance
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The drug research and development nowadays is focusing on multi-target drugs. In the treatment of cancer, therapies using drugs inhibiting one numerous targets signify a novel viewpoint. In comparison with traditional therapy, multi-targeted drugs directly aim cell subpopulations which are involved in progression of tumor. The current study comprises the synthesis of 34 novel ligustrazine-containing α, β-unsaturated carbonyl-based compounds and oximes. The growth of 5 various cancer cell types was strongly inhibited by ligustrazine-containing oximes as revealed by biological evaluation. A strong SAR was provided by the antiproliferative activity. The mechanistic effects of most active antiproliferative compounds on tubulin polymerization, EGFR TK kinases, KAF and BRAFV600E were investigated, followed by in?vitro investigation of reversal of efflux-based resistance developed by cancer cells. EGFR was strongly inhibited by two oximes 7e and 8o. Out of all linkers including positive control, 1-isopropyl-piperidin-4-one linker-bearing compounds showed best inhibition of FAK. The strongest inhibitory activity of BRAFV600E was showed by compound 5e with an IC50 of 0.7?μM. Analogs such as 5 and 7 (b,e,f) exhibited a dual role as anticancer as well as MDR reversal agents. For understanding the target protein integrations with new compounds, molecular docking studies were also carried out.
- Zha, Gao-Feng,Qin, Hua-Li,Youssif, Bahaa G.M.,Amjad, Muhammad Wahab,Raja, Maria Abdul Ghafoor,Abdelazeem, Ahmed H.,Bukhari, Syed Nasir Abbas
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- Synthesis and relationship of stability and biological activity of new DSS and TMP conjugates
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A series of novel conjugates of danshensu (DSS) and tetramethylpyrazine (TMP) were designed and synthesized. Their stability toward hydrolysis by carboxylesterase and cardioprotective effect against t-BHP- and doxorubicin-induced damage were evaluated in H9c2 cells. The results revealed that increasing steric hindrance with bulky groups at the linkage position between DSS and TMP prolonged the half-life and also markedly increased the protective effect. Compound 7 was the most potent in protecting against t-BHP- and doxorubicin-induced damage. The protective effect of compound 7 may in part be attributed to its promotion of mitochondrial biogenesis. This journal is
- Sun, Yewei,Tan, Zicheng,Liang, Zhibin,Wang, Liang,Shan, Luchen,Yu, Pei,Lee, Simon Mingyuen,Wang, Yuqiang
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- Synthesis and biological evaluation of ligustrazine derivatives
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Synthesized ligustrazine derivatives (1a, 1b, 1c (novel)) were structurally confirmed by mass spectrometry,1H NMR, and 13C NMR. The cytotoxic activities of all derivatives were evaluated by MTS assay in three human prostate cancer cell lines (PC-3, LNCaP, and DU145) and in the A549 human lung cancer cell line. Compound 1a exhibited strong cytotoxic activity against PC-3 cells (IC50 3.63μM). In addition, compounds 1-1c showed moderate α1-adrenergic receptor (AR) subselective antagonistic and β2-AR agonistic effects, indicating potential use for the treatment of chronic obstructive pulmonary disease. Molecular docking results showed 1b bound to one region of the active site in β2-AR, but 1, 1a, and 1c bound to a different region.
- Zhang, Chao,Chen, Lang-Di,Liang, Xin-Tong,Liu, Wei-Xiong,Wu, Wen-Hao
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- Synthesis and biological evaluation of novel ligustrazine-chalcone derivatives as potential anti-triple negative breast cancer agents
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A series of novel ligustrazine-chalcone hybrids were synthesized and evaluated for their in vitro and in vivo antitumor activities. The results showed that most of these compounds exhibited significant in vitro cytotoxicity against MDA-MB-231, MCF-7, A549
- Chen, Shaobin,Huang, Jianan,Huang, Qinghui,Li, Yuanzhi,Luo, Yingqi,Wang, Chengxu,Wu, Wenhao,Yu, Lihong,Zha, Dailong,Zhang, Chao,Zhang, Jianye,Zhou, Wenmin
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- Discovery of a new tetramethylpyrazine based chalcone with α, β-unsaturated ketone moiety as a potential anticancer agent
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In this study, a new ligustrazine-based chalcone molecule has been synthesized that contains an extra α, β-Unsaturated ketone moiety along with α, the β-Unsaturated carbonyl group of chalone. A new tetramethylpyrazine (TMP) based aldehyde was synthesized to make the TMP (ligustrazine) as part of chalcone and then it was reacted with newly synthesized ketone containing additional α, β-Unsaturated ketone moiety. After characterization, this new compound was evaluated for its effect on different types of cancer cell lines and very promising results were obtained. The growth of these cancer cells was inhibited by newly designed and synthesized compounds, especially for colon and pancreatic cancer cells with IC50 0.04-0.05 μM.
- Bukhari, Syed Nasir Abbas
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p. 826 - 829
(2020/02/25)
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- Chloroxime compound as well as preparation method and application thereof in pharmacy
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The invention relates to a chloroxime compound, its preparation method and application in pharmacy. The chloroxime compound has a structure shown as the general formula I in the specification. The compounds has a very strong effect in synergistic regulation of heat shock protein activity, can be used for treating neurodegenerative diseases caused by injection of Abeta1-42 to rats, and aims to treat human neurodegenerative diseases. The compound also has a significant stress resistant effect, and can be used for preparation of new drugs treating diseases caused by protein misfolding and/or aggregation, and oxidative stress.
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- TRIFLUOROACETYL HYDRAZIDE COMPOUNDS AND MEDICAL USES THEREOF
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The present invention relates to trifluoroacetyl hydrazide compounds and medical uses thereof. The compounds have a structure of the following formula: The compounds showed multifunctional mechanisms, including inhibition of glutamate excitotoxicity, activation of MEF2 transcriptional activity, clearance of free radicals, and promotion of nerve differentiation, and has a better protective effect on cells especially nerve cells. The compound can be used to prepare prophylactic or therapeutic medicaments with cytoprotective effects, for the prevention or treatment of diseases related to glutamate receptor activation, MEF2 disorders or excessive free radicals generation. The diseases include, for example, neurodegenerative diseases such as Alzheimer's disease, Parkinson and stroke, and the free radicals related diseases such as heart disease, myocardial ischemia, diabetes and other cardiovascular and cerebrovascular diseases.
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- Novel Ligustrazine-Based Analogs of Piperlongumine Potently Suppress Proliferation and Metastasis of Colorectal Cancer Cells in Vitro and in Vivo
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Piperlongumine 1 increases reactive oxygen species (ROS) levels and preferably induces cancer cell apoptosis by triggering different pathways. However, the poor solubility of 1 limits its intensive investigation and clinical application. Ligustrazine possesses a water-soluble pyrazine skeleton and can inhibit proliferation and metastasis of cancer cells. We synthesized compound 3 by replacement of the trimethoxyphenyl of 1 with ligustrazine moiety and further introduced 2-Cl, -Br, and -I to 3 for synthesis of 4-6, respectively. Compound 4 possessed 14-fold greater aqueous solubility than 1 and increased ROS levels in colorectal cancer HCT-116 cells. Additionally, 4 preferably inhibited proliferation, migration, invasion, and heteroadhesion of HCT-116 cells. Treatment with 4 suppressed tumor growth and lung metastasis in vivo and prolonged the survival of tumor-bearing mice. Furthermore, 4 mitigated TGF-β1-induced epithelial-mesenchymal transition and Wnt/β-catenin activation by inhibiting the Akt and GSK-3β phosphorylation in HCT-116 cells. Collectively, 4 displayed significant antiproliferation and antimetastasis activities, superior to 1.
- Zou, Yu,Zhao, Di,Yan, Chang,Ji, Yanpeng,Liu, Jin,Xu, Jinyi,Lai, Yisheng,Tian, Jide,Zhang, Yihua,Huang, Zhangjian
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p. 1821 - 1832
(2018/03/21)
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- Ligustrazine chalcone compound and preparation method and application thereof
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The invention relates to a ligustrazine chalcone compound and a preparation method and application thereof. The ligustrazine chalcone compound is an antioxidant with a series of novel structure, and better antioxidation activities are shown by most of compounds, so that the ligustrazine chalcone compound has further studying and developing value, and the ligustrazine chalcone compound can be usedas a lead compound of the antioxidant. The invention further provides the application of preparing antioxidation medicines of the compound and a composition containing one or more compounds.
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- Synthesis and biological evaluation of new tetramethylpyrazine-based chalcone derivatives as potential anti-Alzheimer agents
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In the current study, a series of new ligustrazine-based chalcones was synthesized. For insertion of tetramethylpyrazine (TMP, also designated as ligustrazine) in chemical backbone of chalcone, a new ligustrazine-based aldehyde was prepared. New ketones were synthesized for inclusion of quinazolin-4-yl amino and pyrazin-2-yl amino moieties. The newly synthesized compounds were screened for acetylcholinesterase, butyrylcholinesterase, and monoamine oxidases (MAO) inhibitory activities and also for in vitro cytotoxicity on PC12 cells. The effect of these compounds against amyloid β-induced cytotoxicity and aggregation was also investigated. The synthesized compounds effectively inhibited the related enzymes and also exhibited neuroprotective effects. Most of the compounds displayed better inhibitory potencies against Aβ aggregation than reference compounds. Some compounds such as 11e and 16b showed very potent effects on multiple targets exhibiting behavior as multifunctional anti-Alzheimer agents.
- Wang, Meng,Qin, Hua-Li,Leng, Jing,Ameeduzzafar,Amjad, Muhammad Wahab,Raja, Maria Abdul Ghafoor,Hussain, Muhammad Ajaz,Bukhari, Syed Nasir Abbas
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p. 1859 - 1866
(2018/07/31)
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- TRIFLUOROACETYL HYDRAZIDE COMPOUNDS AND METHODS OF PREPARATION AND USES THEREOF
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The present invention relates to trifluoroacetyl hydrazide compounds and methods of preparation and uses thereof. The compounds have a structure of the following formula: The compounds showed multifunctional mechanisms, including inhibition of glutamate excitotoxicity, activation of MEF2 transcriptional activity, clearance of free radicals, and promotion of nerve differentiation, and has a better protective effect on cells especially nerve cells. The compound can be used to prepare prophylactic or therapeutic medicaments with cytoprotective effects, for the prevention or treatment of diseases related to glutamate receptor activation, MEF2 disorders or excessive free radicals generation. The diseases include, for example, neurodegenerative diseases such as Alzheimer's disease, Parkinson and stroke, and the free radicals related diseases such as heart disease, myocardial ischemia, diabetes and other cardiovascular and cerebrovascular diseases.
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- A kind of Rhizoma Chuanxiong oxadiazine derivatives, preparation method and application thereof (by machine translation)
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The invention relates to the field of pharmaceutical chemistry, and in particular relates to a kind of Rhizoma Chuanxiong oxadiazine derivatives (I) and (II) and its preparation method, the pharmacodynamics tests prove that, Rhizoma Chuanxiong oxadiazine derivatives of this invention has a certain anti-tumor activity and significant inhibition of tumor cell migration and attack role, can be used for the treatment of tumor. (by machine translation)
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- Compound containing ligustrazine chalcone aryloxy acids and preparing method and application of compound
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The invention relates to the field of medical chemistry, in particular to a compound (I) containing ligustrazine chalcone aryloxy acids and a preparing method of the compound. It is proved through pharmacodynamic tests that the compound has the medical application of treating hyperlipidemia and antherosclerosis. The formula is shown in the specification.
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- Discovery of New Monocarbonyl Ligustrazine-Curcumin Hybrids for Intervention of Drug-Sensitive and Drug-Resistant Lung Cancer
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The elevation of oxidative stress preferentially in cancer cells by inhibiting thioredoxin reductase (TrxR) and/or enhancing reactive oxygen species (ROS) production has emerged as an effective strategy for selectively targeting cancer cells. In this study, we designed and synthesized 21 ligustrazine-curcumin hybrids (10a-u). Biological evaluation indicated that the most active compound 10d significantly inhibited the proliferation of drug-sensitive (A549, SPC-A-1, LTEP-G-2) and drug-resistant (A549/DDP) lung cancer cells but had little effect on nontumor lung epithelial-like cells (HBE). Furthermore, 10d suppressed the TrxR/Trx system and promoted intracellular ROS accumulation and cancer cell apoptosis. Additionally, 10d inhibited the NF-κB, AKT, and ERK signaling, P-gp-mediated efflux of rhodamine 123, P-gp ATPase activity, and P-gp expression in A549/DDP cells. Finally, 10d repressed the growth of implanted human drug-resistant lung cancer in mice. Together, 10d acts a novel TrxR inhibitor and may be a promising candidate for intervention of lung cancer.
- Ai, Yong,Zhu, Bin,Ren, Caiping,Kang, Fenghua,Li, Jinlong,Huang, Zhangjian,Lai, Yisheng,Peng, Sixun,Ding, Ke,Tian, Jide,Zhang, Yihua
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p. 1747 - 1760
(2016/03/25)
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- COMPOUNDS WITH NEURAL PROTECTIVE EFFECT, AND PREPARATION AND USE THEREOF
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The invention generally relates to compounds of formula (I) with neural protective effect, and preparation and uses thereof. The compounds have multiple mechanisms or functions, for example, inhibition of monoamine oxidase and cholinesterase, scavenging of free radicals, and protection of cells such as nerve cells. The compounds can be used for manufacture of medicaments of cell protection, for prevention and/or treatment of monoamine oxidase, cholinesterase and free radicals related diseases, for example, neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and stroke, and free-radical related diseases such as heart disease, myocardial ischemia, diabetes and other cardiovascular and cerebrovascular diseases.
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- COMPOUNDS WITH NEURAL PROTECTIVE EFFECT, AND PREPARATION AND USE THEREOF
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The invention generally relates to compounds of formula (I) with neural protective effect, and preparation and uses thereof. The compounds have multiple mechanisms or functions, for example, inhibition of monoamine oxidase and cholinesterase, scavenging of free radicals, and protection of cells such as nerve cells. The compounds can be used for manufacture of medicaments of cell protection, for prevention and/or treatment of monoamine oxidase, cholinesterase and free radicals related diseases, for example, neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and stroke, and free-radical related diseases such as heart disease, myocardial ischemia, diabetes and other cardiovascular and cerebrovascular diseases.
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- Ligustrazine Derivatives. Part 4: Design, Synthesis, and Biological Evaluation of Novel Ligustrazine-based Stilbene Derivatives as Potential Cardiovascular Agents
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A series of novel stilbene derivatives containing ligustrazinyl moiety was designed, synthesized, and assayed for their protective effects on damaged endothelial cells. The results showed that most ligustrazinyl stilbene derivatives exhibited high protective effects on the human umbilical vascular endothelial cells (HUVECs) damaged by hydrogen peroxide in comparison with Ligustrazine. The stilbene derivatives A6, A9, A11, A21, A24, A25, and A27 exhibited high potency with low EC50 values ranged from 0.0249μm to 0.0898mm. Compound A27 displayed EC50 0.0249μm, which is 30000 times higher than that of Ligustrazine, presenting a most promising lead for further investigation. Structure-activity relationships were briefly discussed.
- Deng, Lijuan,Guo, Xiuli,Zhai, Li,Song, Yuning,Chen, Hongfei,Zhan, Peng,Wu, Jingde,Liu, Xinyong
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p. 731 - 739
(2012/05/20)
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- PYRAZOLOPYRIMIDINE COMPOUNDS AND THEIR USE AS PDE10 INHIBITORS
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The present invention relates to a compound represented by formula [I]: wherein: R1 is hydrogen, halogen, lower alkyl or cyano; Ring A is an optionally substituted heterocyclic group; Ring B is an optionally substituted 3 to 6-membered monocyclic group; and Y is optionally substituted amino, optionally substituted cyclic amino, optionally substituted aliphatic 3 to 6-membered monocyclyloxy, optionally substituted lower alkyl or optionally substituted lower alkyl-O-, or a pharmaceutically acceptable salt thereof, and to their use as PDE10 inhibitor.
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Page/Page column 78
(2011/09/30)
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