CN113577061A - 七甲川吲哚类花菁染料ir-61在制备抑制病菌生长的药物中的应用 - Google Patents
七甲川吲哚类花菁染料ir-61在制备抑制病菌生长的药物中的应用 Download PDFInfo
- Publication number
- CN113577061A CN113577061A CN202110800702.8A CN202110800702A CN113577061A CN 113577061 A CN113577061 A CN 113577061A CN 202110800702 A CN202110800702 A CN 202110800702A CN 113577061 A CN113577061 A CN 113577061A
- Authority
- CN
- China
- Prior art keywords
- cyanine dye
- heptamethine
- mol
- indole cyanine
- bacteria
- 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.)
- Pending
Links
Images
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
- A01N43/38—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings condensed with carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pest Control & Pesticides (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Plant Pathology (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- Wood Science & Technology (AREA)
- Agronomy & Crop Science (AREA)
- Environmental Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
本发明涉及七甲川吲哚类花菁染料IR‑61在制备抗病菌的药物中的应用。所述七甲川吲哚类花菁染料IR‑61对黄色葡萄球菌、表皮葡萄球菌及大肠杆菌的最低抑菌浓度(MIC)分别为20μmol/L、20μmol/L、40μmol/L。细菌电镜实验证明花菁染料IR‑61在细菌生长过程中会破坏其细胞壁,使细胞壁形态发生变化,菌落周围出现透明降解圈,实现对金黄色葡萄球菌、表皮葡萄球菌及大肠杆菌的抑制。
Description
技术领域
本发明涉及一种药物应用,特别涉及一种七甲川吲哚类花菁染料IR-61在制备抑制病菌生长的药物中的应用。
背景技术
抗生素的发现和发展极大地降低了感染的发病率和病死率,但随着抗生素的不合理使用甚至是滥用,细菌的耐药性不断增强,导致许多抗生素失去了原有的疗效,感染性疾病的治疗面临巨大的挑战。世界卫生组织等监管机构宣布,抗生素的耐药性正在对全球健康构成威胁。近年来抗生素的研发多集中在已有抗生素的结构改造和性能优化上,常规抗生素的研发速度已经跟不上细菌产生耐药性的速度,所取得的进展十分有限,无法有效地控制抗生素耐药性的发展,因此迫切需要发展新结构、新作用机制的抗菌药物以克服细菌耐药性问题,加快对新型抗菌药物的开发和利用迫在眉睫。
吲哚七甲川花菁类染料是由多聚甲炔构成的具有多共轭结构的含氮杂环化合物,其最大吸收和发射波长在近红外区(700-900nm),具有近红外荧光(near-infared,NIR)成像能力。由于在近红外区间,生物组织吸收以及自发荧光强度低,因而将其作为显影剂,具有背景干扰小、灵敏性高、非侵袭性等优点。更重要的是,这类化合物还具有组织特异性靶向定位性能,使其在生物、医疗、光学材料等领域均得到广泛应用。然而,该类化合物在抗病菌方面的作用尚未见报道。
发明内容
本发明的目的是提供一种七甲川吲哚类花菁染料IR-61在制备抑制病菌生长的药物中的应用,所述七甲川吲哚类花菁小分子化合物IR-61(以下称七甲川吲哚类花菁染料IR-61或简称为IR-61)对多种病菌显示出抗菌活性,特别是对金黄色葡萄球菌、表皮葡萄球菌及大肠杆菌均有较强的抗菌作用。
本发明的技术方案是:
七甲川吲哚类花菁染料IR-61在制备抑制病菌生长的药物中的应用。
所述病菌为球菌或杆菌。
所述球菌为金黄色葡萄球菌或表皮葡萄球菌。
所述杆菌为大肠杆菌。
所述七甲川吲哚类花菁染料IR-61的结构是为:
七甲川吲哚类花菁染料IR-61对金黄色葡萄球菌的最低抑菌浓度为20μmol/L。
七甲川吲哚类花菁染料IR-61对表皮葡萄球菌的最低抑菌浓度为20μmol/L。
七甲川吲哚类花菁染料IR-61对大肠杆菌的最低抑菌浓度为40μmol/L。
所述药物为抑制剂。
申请人实验证明七甲川吲哚类花菁染料IR-61在细菌生长过程中会破坏其细胞壁,使细胞壁形态发生变化,菌落周围出现透明降解圈,说明其对金黄色葡萄球菌、表皮葡萄球菌及大肠杆菌的抑制。本发明所述七甲川吲哚类花菁染料IR-61对黄色葡萄球菌、表皮葡萄球菌及大肠杆菌的最低抑菌浓度(MIC)分别为20μmol/L、20μmol/L、40μmol/L。
附图说明
图1-1为20μM IR-61处理金黄色葡萄球菌的生长曲线;
图1-2为20μM IR-61处理表皮葡萄球菌的生长曲线;
图1-3为40μM IR-61处理大肠杆菌的生长曲线;
图2为金黄色葡萄球菌对照组电镜图(左)及IR-61处理电镜图(右);
图3为表皮葡萄球菌对照组电镜图(左)及IR-61处理电镜图(右);
图4为大肠杆菌对照组电镜图(左)及IR-61处理电镜图(右)。
具体实施方式
1.试剂:
戊二醛购于阿拉丁公司;细菌培养基MHB购于sigma公司;PBS粉剂购于博士德生物公司;金黄色葡萄球菌-ATCC25923、表皮葡萄球菌-ATCC12228、大肠杆菌-ATCC25922均购于ATTCC公司。
实验所用平皿、离心管、枪头均购自Corning公司。
2.仪器:
纯水仪(型号GE,美国);低温高速离心机(型号:ST16,Thermo美国);生物安全柜(型号:1300A2,Thermo美国);细菌恒温培养箱(型号:UF110,德国);多功能酶标仪(型号:M2e,MD,德国);高压灭菌锅(型号:SN210C,yamato,日本);恒温摇床(型号:ZWY-240,上海圣科,中国);电子天平(型号:BSA124S,德国);恒温磁力搅拌器(型号:S10-2,中国);透射电镜(型号:JEM-1400Plus,日本)。
七甲川吲哚类花菁染料IR-61,结构式如下所示:
所述的七甲川吲哚类花菁染料IR-61按照专利号CN201710144214所述方法制备得到。
实施例1最低抑菌浓度
本实验所用细菌如表1所示:
表1实验材料
细菌活化:取本实验室-80℃甘油保存的大肠杆菌、金黄色葡萄球菌、表皮葡萄球菌,融化后,分别按照1:1000的比例稀释,取10ul滴到MHB固体培养基上面,三线法划板后,倒置放入恒温培养箱,12h后挑单克隆菌落,37℃,220r/min,震荡过夜,做为种子液4℃保存。
最低抑菌浓度(MIC)的测定
实验方法:
1)灭菌枪头挑取单克隆金黄色葡萄球菌、表皮葡萄球菌及大肠杆菌分别接种至10mL灭菌MHB培养基中,37℃恒温摇床,220r/min,过夜培养;
2)吸取100μL细菌悬液接种至10mL灭菌MHB培养基中,37℃恒温摇床,220r/min,2h培养细菌至对数生长期;
3)吸取1mL菌液至离心管中,8000r/min,离心5min;弃去上清液,加入1mL灭菌MHB培养基至离心管中,8000r/min,离心5min,测OD值(MHB培养基的OD值为对照),根据所测OD值逐步稀释细菌浓度至5*105CFU/mL;
4)吸取90μL菌液至离心管,再加入10μL IR-61,37℃恒温摇床,220r/min,24h培养,测OD值;
表2MIC的测定结果
C<sub>IR-61</sub>/μM | S au | S ep | E co |
5 | + | + | + |
10 | + | + | + |
20 | — | — | + |
40 | — | — | — |
注:“+”有菌生长;“—”无菌生长。
七甲川吲哚类花菁染料IR-61对于金黄色葡萄球菌及表皮葡萄球菌的最低抑菌浓度为20μmol/L,抗菌效果较好。
实施例2生长曲线的测定
分别取100ul活化后的大肠杆菌、金黄色葡萄球菌、表皮葡萄球菌种子液至10ml无菌MHB培养基中,37℃,220r/min,2h,细菌培养至对数生长期(OD=0.5);取1ml上述菌液至1.5ml离心管中,8000rmp,4℃低温离心5min;弃上清,用1ml新鲜MHB培养基重悬细菌,测OD值后,稀释细菌浓度为1×10*8CFU/ml,然后依次稀释十倍,直至稀释到5×10*5CFU/ml;菌液稀释好后,加入96孔板,每孔加入180ul菌液,补充20ul的IR61,金黄色葡萄球菌和表皮葡萄球菌对应IR61浓度为20μmol/L,大肠杆菌对应IR61浓度为40μmol/L;放入于MD2e多功能酶标仪检测细菌生长曲线。参数设置如下:动态检测,温度37℃,OD600总时长20h,10min间隔读数,首次读数前震荡5s,后续读数前每次震荡30s,记录细菌OD600数值,做生长曲线。
生长曲线的测定结果如下:
(1)由图1-1及图1-2可知,对于金黄色葡萄球菌和表皮葡萄球菌,20μmol/L的IR-61在7h内可以抑制其生长,7h后细菌数量开始增多,逐渐进入平台期;
(2)由图1-3可知,对于大肠杆菌,40μmol/L的IR-61在3h内可以抑制其生长,3h后细菌数量开始增多。
实施例3电镜实验
电镜实验结果:
电镜样本制备:分别取100ul活化后的大肠杆菌、金黄色葡萄球菌、表皮葡萄球菌种子液至10ml无菌MHB培养基中,37℃,220r/min,2h,细菌培养至对数生长期(OD=0.5);取1ml上述菌液至1.5ml离心管中,8000rmp,4℃低温离心5min;弃上清,用1ml新鲜MHB培养基重悬细菌,测OD值后,稀释细菌浓度为1×10*8CFU/ml,然后依次稀释十倍,直至稀释到5×10*5CFU/ml;菌液稀释好后,取菌液450ul和50ul的IR61,金黄色葡萄球菌和表皮葡萄球菌对应IR61浓度为20μmol/L,大肠杆菌对应IR61浓度为40μmol/L,补充新鲜MHB至5ml,37℃,220r/min,12h;8000rpm离心8min,弃上清,PBS洗2遍,菌液置于1.5mlEP管内用2.5%戊二醛固定,4℃过夜;按照常规TEM样品制备方法依次进行漂洗、脱水、浸透、切片、染色,JEM-1400Plus透射电镜观察。
电镜实验结果:由图2、3、4可知,与对照组相比,七甲川吲哚类花菁染料IR-61在细菌生长过程中会破坏其细胞壁,使细胞壁形态发生变化,菌落周围出现透明降解圈,从而实现对金黄色葡萄球菌、表皮葡萄球菌及大肠杆菌的抑制。
Claims (9)
1.七甲川吲哚类花菁染料IR-61在制备抑制病菌生长的药物中的应用。
2.根据权利要求1所述的应用,其特征在于:所述病菌为球菌或杆菌。
3.根据权利要求2所述的应用,其特征在于:所述球菌为金黄色葡萄球菌或表皮葡萄球菌。
4.根据权利要求2所述的应用,其特征在于:所述杆菌为大肠杆菌。
6.根据权利要求3所述的应用,其特征在于:七甲川吲哚类花菁染料IR-61对金黄色葡萄球菌的最低抑菌浓度为20μmol/L。
7.根据权利要求3所述的应用,其特征在于:七甲川吲哚类花菁染料IR-61对表皮葡萄球菌的最低抑菌浓度为20μmol/L。
8.根据权利要求4所述的应用,其特征在于:七甲川吲哚类花菁染料IR-61对大肠杆菌的最低抑菌浓度为40μmol/L。
9.根据权利要求1所述的应用,其特征在于:所述药物为抑制剂。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110800702.8A CN113577061A (zh) | 2021-07-15 | 2021-07-15 | 七甲川吲哚类花菁染料ir-61在制备抑制病菌生长的药物中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110800702.8A CN113577061A (zh) | 2021-07-15 | 2021-07-15 | 七甲川吲哚类花菁染料ir-61在制备抑制病菌生长的药物中的应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN113577061A true CN113577061A (zh) | 2021-11-02 |
Family
ID=78247670
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202110800702.8A Pending CN113577061A (zh) | 2021-07-15 | 2021-07-15 | 七甲川吲哚类花菁染料ir-61在制备抑制病菌生长的药物中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113577061A (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023274003A1 (zh) * | 2021-07-01 | 2023-01-05 | 中国人民解放军陆军军医大学 | 一种七甲川吲哚花菁或其衍生物的抗菌用途 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106511337A (zh) * | 2016-09-23 | 2017-03-22 | 中国人民解放军第三军医大学 | 一类七甲川吲哚花菁染料的应用 |
CN112587521A (zh) * | 2020-11-24 | 2021-04-02 | 扬州大学 | 花菁类染料ir780的抗菌新用途 |
WO2021086982A2 (en) * | 2019-10-28 | 2021-05-06 | Beckman Coulter, Inc. | Compounds for the identification of microbial classes and uses thereof |
-
2021
- 2021-07-15 CN CN202110800702.8A patent/CN113577061A/zh active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106511337A (zh) * | 2016-09-23 | 2017-03-22 | 中国人民解放军第三军医大学 | 一类七甲川吲哚花菁染料的应用 |
WO2021086982A2 (en) * | 2019-10-28 | 2021-05-06 | Beckman Coulter, Inc. | Compounds for the identification of microbial classes and uses thereof |
CN112587521A (zh) * | 2020-11-24 | 2021-04-02 | 扬州大学 | 花菁类染料ir780的抗菌新用途 |
Non-Patent Citations (2)
Title |
---|
CHI ZHANG等: "Mitochondria-Targeting IR-780 Dye and Its Derivatives: Synthesis, Mechanisms of Action, and Theranostic Applications", 《ADVANCED THERAPEUTICS》 * |
YAWEI WANG等: "Improvement of obesity-associated disorders by a small-molecule drug targeting mitochondria of adipose tissue macrophages", 《NATURE COMMUNICATIONS》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023274003A1 (zh) * | 2021-07-01 | 2023-01-05 | 中国人民解放军陆军军医大学 | 一种七甲川吲哚花菁或其衍生物的抗菌用途 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN109251898B (zh) | 一株金黄色葡萄球菌噬菌体及其应用 | |
CN106929481B (zh) | 一种铜绿假单胞菌噬菌体及其应用 | |
CN113621584B (zh) | 一株金黄色葡萄球菌噬菌体及其抑菌应用 | |
Zhou et al. | A purpurin-peptide derivative for selective killing of Gram-positive bacteria via insertion into cell membrane | |
CN113577061A (zh) | 七甲川吲哚类花菁染料ir-61在制备抑制病菌生长的药物中的应用 | |
CN113025582B (zh) | 一株肺炎克雷伯菌噬菌体及医用用途 | |
CN109880772A (zh) | 一种幽门螺杆菌菌株分离培养的方法 | |
CN114569558B (zh) | 辣木秸秆介导合成生物碲纳米颗粒及其抗菌抗病毒应用 | |
CN113174372B (zh) | 一种噬菌体vB_KpnS_ZH01及医用用途 | |
CN108939146B (zh) | 一种抗菌/抗骨肉瘤/促成骨多功能性钛基植入材料及其制备方法 | |
CN107950537B (zh) | 咪唑类生物碱在治疗植物病毒和病菌中的应用 | |
CN115006546B (zh) | 一种促进伤口愈合的双硫异质结材料及其制备方法 | |
CN109266621B (zh) | 一株新浅绿色气球菌噬菌体avp及其用途 | |
CN110747177A (zh) | 一株鲍曼不动杆菌噬菌体及医用用途 | |
CN110747251A (zh) | 一种抑制病原菌的潜在益生菌株的快速筛选方法 | |
CN116354954A (zh) | 一种靶向溶酶体的aie探针及其制备方法与应用 | |
RU2517121C2 (ru) | Способ повышения качества хирургической нити | |
CN112695017B (zh) | 噬菌体vB_Yen_X1及在防治鼠疫杆菌感染中应用 | |
CN115025044A (zh) | 一种抗菌聚鞣酸纳米粒PTA NPs及其制备方法 | |
Zhang et al. | A nanozyme-reinforced injectable photodynamic hydrogel for combating biofilm infection | |
CN114288405A (zh) | PEG-b-PAA-g-SNO@IR780 NPs纳米粒子在制备抗菌材料上的应用 | |
CN108721248A (zh) | 一种pH响应型纳米银组装体的制备方法、产物及应用 | |
CN111214489A (zh) | 一种抗菌络合物及其在抑制细菌生物被膜方面的应用 | |
CN111979292A (zh) | 一种同时携带多重耐药基因cfr和lsa(E)的MRSA的用途 | |
CN113186169B (zh) | 一株粘质沙雷氏菌噬菌体及医用用途 |
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 |