CN109498608B - 一种海洋来源的二苯醚类活性成分在制备治疗ⅱ型糖尿病药物中的应用 - Google Patents
一种海洋来源的二苯醚类活性成分在制备治疗ⅱ型糖尿病药物中的应用 Download PDFInfo
- Publication number
- CN109498608B CN109498608B CN201810476764.6A CN201810476764A CN109498608B CN 109498608 B CN109498608 B CN 109498608B CN 201810476764 A CN201810476764 A CN 201810476764A CN 109498608 B CN109498608 B CN 109498608B
- Authority
- CN
- China
- Prior art keywords
- active constituent
- diphenyl ether
- diabetes
- application
- drug
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/075—Ethers or acetals
- A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
- A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明公开了一种海洋来源的二苯醚类活性成分在制备治疗Ⅱ糖尿病药物中的应用。首次公开了该二苯醚类活性成分在制备治疗Ⅱ糖尿病中的用途，可有效抑制a‑葡萄糖苷酶，活性成分是来源于海洋丰富的微生物资源的代谢产物，具有低毒、高效、易规模产业化的特性，为目前治疗Ⅱ糖尿病药物提供了一种全新的选择和思路。
Description
技术领域
本发明涉及天然药物化学领域，具体涉及一类源于海洋真菌代谢的二苯醚类活性成分，在制备治疗Ⅱ型糖尿病药物中的应用，属于天然药物领域。
背景技术
Ⅱ型糖尿病是一种严重危害人类健康的慢性非传染性疾病，文献报道糖尿病病程、高血压、高血糖、性别、年龄、高血脂、肥胖及人种均与糖尿病肾病的进展相关。随着社会经济的发展和人们生活方式的改变,糖尿病的发病率逐年迅速上升,己经成为继心脑血管疾病和肿瘤之后的第三大严重危害健康的疾病，我国已成为糖尿病患者第一大国。随着胰岛素、促胰岛素分泌药物、胰岛素增敏剂等药物的不断开发与应用,以及强化治疗方案的提出,糖尿病治疗领域不断进步。但是,而近年的多项调查表明，无论是欧美发达国家还是发展中国家，糖尿病控制状况均不容乐观，目前在临床上仍然缺乏有效的手段控制糖尿病及其并发症的发生与进展。
国际上对Ⅱ型糖尿病药物的研发一直未停歇，但也一直未推出新的特效药能有效地治疗Ⅱ型糖尿病，如果某种新药能缓解或治疗这种疾病，将是对人类的一大贡献。在我国，糖尿病发病率约9.8％，我国的糖尿病患者已超过1亿，给个人、家庭以及社会带来严重负担，已成为一个必须高度重视的公共卫生问题乃至社会问题，而在糖尿病患者中95％以上为Ⅱ型糖尿病。现有的治疗Ⅱ型糖尿病药物中，价格昂贵收效甚微，并多年未有特效药进入市场。进入老年人社会而导致的Ⅱ型糖尿病的高发，还给家庭、社会带来沉重的经济负担。为了避免或减少当前药物的不良副作用或耐药性，同时提供更多候选药物和降低治疗Ⅱ型糖尿病药物的成本，因此寻找新的Ⅱ型糖尿病药物是迫切需要的。
文献(J.Nat.Prod.2015,78,844-849)公开了从海洋来源的真菌代谢产物中分离得到的如下结构的二苯醚类化合物，其报道有较强的抑菌活性。
发明内容
本发明的目的提供上述从海洋来源的真菌代谢产物中分离得到的二苯醚类化合物的新药用用途。
本发明发现该二苯醚类化合物具有显著有效抑制a-葡萄糖苷酶活性的候选药物分子。
一种海洋来源的二苯醚类活性成分在制备治疗Ⅱ型糖尿病药物中的应用；所述二苯醚类活性成分的结构式如下所示：
所述治疗Ⅱ型糖尿病药物可以制备成目前适于人用临床应用的药物制剂，如片剂、胶囊、颗粒剂、注射剂等。
与现有技术相比，本发明具有如下有益效果：
1.本发明为目前Ⅱ型糖尿病药物提供了一种海洋真菌代谢来源的药物小分子，拓宽了治疗Ⅱ型糖尿病药物来源选择和技术参考，为该技术领域的发展作出了贡献。
2.本发明首次公开了Ⅱ型糖尿病药物二苯醚类活性成分peniciaculins A在制备治疗Ⅱ型糖尿病药物中的用途，可显著有效抑制a-葡萄糖苷酶活性。
3.本发明中的Ⅱ型糖尿病药物二苯醚类活性成分peniciaculins A化合物来源于海洋真菌的代谢产物中，具有低毒、高效的特性。
附图说明：
图1为实施例1中对治疗Ⅱ型糖尿病药物二苯醚类活性成分peniciaculins A在不同浓度抑制a-葡萄糖苷酶活性的作用；
图2为潜在治疗Ⅱ型糖尿病药物二苯醚类活性成分peniciaculins A的α-葡萄糖苷酶抑制作用的双倒数酶动力学曲线。
具体实施方式：
实施例1对Ⅱ型糖尿病药物二苯醚类活性成分peniciaculins A进行a-葡萄糖苷酶活性实验。
材料：
阳性对照：acarbose(阿卡波糖，文献中的IC50为(IC50＝545±19μM，此次我们测出的值约为700-800μM)；空白对照：DMSO代替样品。葡萄糖苷酶(厂商阿拉丁，58units/mg,文献中配成的浓度是0.4units/ml,此次试验中，我们称0.58mg溶于10ml磷酸缓冲液，再从中取1ml稀释至10ml,再从稀释后的10ml取1ml稀释至2ml,最终浓度大概为0.2units/ml，现用现配)；基质(即底物PNPG，配置的浓度为5mMol/L，用磷酸缓冲液溶解，现用现配)；葡萄糖苷酶和基质一定要在冷藏室中保温。磷酸缓冲液(pH＝7，100mMol/L，其中磷酸氢二钾占61.5％，磷酸二氢钾占31.5％，此次我们配制了500ml缓冲液。)；样品(事先称量好，用DMSO溶解)；96孔板；2-20，20-200，100-1000μl的移液枪；5-50μl的移液排枪(8排)；3种枪头。酶标仪。
注：只有中间白色区域测试用，灰色区域都空着不放任何东西。
步骤：60μl磷酸缓冲液+20μl葡萄糖苷酶溶液+10μl样品(最后一步混匀)——在37摄氏度的条件反应10min——加10μl基质(混匀)——在37摄氏度的条件反应20min——测量。(酶标仪：单波长405nm)前后顺序不能变，样品的终浓度为原来的十分之一。最后一步的20min根据情况调整。
1测阳性对照的值
根据文献的数据，配置acarbose的浓度为5000μM，6000μM，7000μM，8000μM，第一列，最后一步不加基质，用10μl磷酸缓冲液代替(此次我们只测了5000μM)。
抑制率：[1-((a样+b样+c样)/3-d样)/((a空+b空+c空)/3-d空)]*100％
2初筛
此次试验初筛的浓度是500μM，即要配成5000μM。先每个样平行两次测试，计算抑制率进行初筛。一般来说，抑制率在50％左右，其IC50大概也就在400-700之间，看情况估计。如果抑制率超过60％，尤其是〉80％就进行下一步梯度测试。
3梯度测试
将进一步测试的样品进行梯度稀释(逐一稀释2倍，则在前者中取50μl再加50μlDMSO，以此稀释5个梯度)，平行三次，进行测试，分别计算5个梯度的抑制率(抑制率在50％上下都有点才合适)，做出曲线，拟合，在曲线上找到抑制率50％对应的浓度就是IC50。
表1.Ⅱ型糖尿病药物peniciaculins A的a-葡萄糖苷酶活性实验
Claims (2)
1.一种海洋来源的二苯醚类活性成分在制备治疗Ⅱ型糖尿病药物中的应用；所述二苯醚类活性成分的结构式如下所示：
2.如权利要求1所述的应用，其特征在于，所述药物的制剂为片剂、胶囊、颗粒剂或注射剂。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810476764.6A CN109498608B (zh) | 2018-05-18 | 2018-05-18 | 一种海洋来源的二苯醚类活性成分在制备治疗ⅱ型糖尿病药物中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810476764.6A CN109498608B (zh) | 2018-05-18 | 2018-05-18 | 一种海洋来源的二苯醚类活性成分在制备治疗ⅱ型糖尿病药物中的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109498608A CN109498608A (zh) | 2019-03-22 |
| CN109498608B true CN109498608B (zh) | 2019-09-20 |
Family
ID=65745562
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810476764.6A Active CN109498608B (zh) | 2018-05-18 | 2018-05-18 | 一种海洋来源的二苯醚类活性成分在制备治疗ⅱ型糖尿病药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109498608B (zh) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR0215936A (pt) * | 2002-10-29 | 2005-08-30 | Council Of Scient & Ind Reseac | Inibidores da alfa-glucosidase a partir de uma fonte natural |
-
2018
- 2018-05-18 CN CN201810476764.6A patent/CN109498608B/zh active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN109498608A (zh) | 2019-03-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| García Rubiño et al. | Phenformin as an anticancer agent: challenges and prospects | |
| Cejuela et al. | Metformin and breast cancer: where are we now? | |
| Dou et al. | Endothelial toxicity of high glucose and its by-products in diabetic kidney disease | |
| Chen et al. | The traditional Chinese medicine DangguiBuxue Tang sensitizes colorectal cancer cells to chemoradiotherapy | |
| Basak et al. | SGLT2 inhibitors as potential anticancer agents | |
| Nocquet et al. | Mitochondria at center of exchanges between cancer cells and cancer-associated fibroblasts during tumor progression | |
| El-Huneidi et al. | The coffee diterpene, kahweol, ameliorates pancreatic β-cell function in streptozotocin (STZ)-treated rat INS-1 cells through NF-kB and p-AKT/Bcl-2 pathways | |
| Vitali et al. | Metformin and everolimus: a promising combination for neuroendocrine tumors treatment | |
| Sayour et al. | Effects of SGLT2 Inhibitors beyond Glycemic Control—Focus on Myocardial SGLT1 | |
| Hori et al. | Hyperthermia enhances the effect of β-lapachone to cause γH2AX formations and cell death in human osteosarcoma cells | |
| Li et al. | SWL-1 reverses fluconazole resistance in Candida albicans by regulating the glycolytic pathway | |
| Kreisel et al. | Phosphodiesterases in the liver as potential therapeutic targets of cirrhotic portal hypertension | |
| Marini et al. | Metformin and cancer glucose metabolism: At the bench or at the bedside? | |
| Salvoza et al. | The beneficial effects of triterpenic acid and acteoside in an in vitro model of nonalcoholic steatohepatitis (NASH) | |
| Casertano et al. | Evidence of insulin-sensitizing and mimetic activity of the sesquiterpene quinone avarone, a protein tyrosine phosphatase 1B and aldose reductase dual targeting agent from the marine sponge Dysidea avara | |
| Xu et al. | Ceramide synthase 1 inhibits brain metastasis of non-small cell lung cancer by interacting with USP14 and downregulating the PI3K/AKT/mTOR signaling pathway | |
| Peyton et al. | Canagliflozin inhibits human endothelial cell inflammation through the induction of heme oxygenase-1 | |
| Ali et al. | Inhibition of aldose reductase by ginsenoside derivatives via a specific structure activity relationship with kinetics mechanism and molecular docking study | |
| Kaushik et al. | Blockade of cellular energy metabolism through 6-aminonicotinamide reduces proliferation of non-small lung cancer cells by inducing endoplasmic reticulum stress | |
| CN109498608B (zh) | 一种海洋来源的二苯醚类活性成分在制备治疗ⅱ型糖尿病药物中的应用 | |
| Li et al. | Dual effect of tryptamine on prostate cancer cell growth regulation: A pilot study | |
| Zhao et al. | A novel derivative of curcumol, HCL-23, inhibits the malignant phenotype of triple-negative breast cancer and induces apoptosis and HO-1-dependent ferroptosis | |
| Della Sala et al. | Unveiling metabolic vulnerability and plasticity of human osteosarcoma stem and differentiated cells to improve cancer therapy | |
| Poursoltani et al. | Sulindac and vitamin D3 synergically inhibit proliferation of MCF‐7 breast cancer cell through AMPK/Akt/β‐catenin axis in vitro | |
| Zhang et al. | Sepsis management in the cardiac intensive care unit |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |