Nystatin
描述
准备方法
制霉菌素通常从诺氏链霉菌发酵液中使用水溶性有机溶剂提取。 然后纯化结晶 . 制霉菌素的工业生产包括发酵、提取、纯化和结晶等一系列步骤，以获得高产率和高纯度的制霉菌素晶体 .
化学反应分析
制霉菌素经历各种化学反应，包括氧化和还原。 该化合物由于存在羧基和氨基而呈两性 . 它实际上不溶于水，但略微溶于极性有机溶剂 . 制霉菌素在水性有机体系中的溶解度增加，在含 30-40% 水的溶液中溶解度最高 .
科学研究应用
Treatment of Oral Candidiasis
Nystatin is commonly used for treating oral candidiasis, especially in immunocompromised patients. A systematic review indicated that this compound pastilles demonstrated a higher clinical cure rate (87%) compared to this compound suspension (80%) in patients with denture stomatitis .
Efficacy Comparison Table:
| Treatment Type | Clinical Cure Rate (%) | Mycological Cure Rate (%) |
|---|---|---|
| This compound Pastilles | 87 | Not specified |
| This compound Suspension | 80 | Not specified |
| Fluconazole | 88 | Not specified |
Prophylaxis in Immunocompromised Patients
This compound has been investigated for prophylactic use in severely immunodepressed patients, such as those undergoing chemotherapy or organ transplantation. However, studies have shown that its efficacy is often inferior to fluconazole, with this compound demonstrating no significant advantage over placebo in preventing fungal colonization .
Prophylaxis Effectiveness Table:
| Study Group | This compound Efficacy | Fluconazole Efficacy | Placebo Efficacy |
|---|---|---|---|
| Acute leukemia patients | No significant difference | Superior | No significant difference |
| Solid cancer patients | No significant difference | Superior | No significant difference |
| Bone marrow transplant recipients | No significant difference | Superior | No significant difference |
Treatment of Cutaneous Infections
This compound is also effective against cutaneous candidiasis and other superficial fungal infections. In cases where patients exhibit hypersensitivity to fungi, this compound has shown superior efficacy compared to placebo in reducing localized and systemic symptoms .
Case Studies
-
Oral Candidiasis in Cancer Patients
A study involving hospitalized cancer patients found that the combination of this compound suspension and pastilles resulted in clinical and mycological cures in 87.5% and 66% of cases, respectively . This highlights this compound's effectiveness in vulnerable populations. -
Fungal Hypersensitivity
In a randomized trial with polysymptomatic patients suspected of having fungus hypersensitivity, this compound significantly reduced overall symptom scores compared to placebo (P < 0.003). This suggests potential benefits beyond traditional antifungal applications .
Safety and Side Effects
While this compound is generally well-tolerated, some common side effects include gastrointestinal discomfort and a poor taste associated with oral formulations. These adverse effects can impact patient adherence to treatment regimens .
作用机制
相似化合物的比较
生物活性
Nystatin is a polyene antifungal agent primarily used to treat fungal infections, particularly those caused by Candida species. Its biological activity is characterized by its mechanism of action, efficacy in clinical applications, and safety profile. This article delves into these aspects, supported by research findings, data tables, and case studies.
This compound exerts its antifungal effects through a unique mechanism involving the binding to ergosterol, a key component of fungal cell membranes. This interaction leads to the formation of pores in the membrane, disrupting its integrity and causing leakage of intracellular contents. The selectivity for fungal cells over mammalian cells is attributed to this compound's higher affinity for ergosterol compared to cholesterol found in human cells .
Key Findings on Mechanism
- Pore Formation : this compound forms membrane-spanning channels that increase permeability, allowing ions and small molecules to leak out, which disrupts essential cellular functions .
- Killing Kinetics : Studies show that this compound exhibits rapid killing kinetics against Candida albicans, with significant reductions in colony-forming units (CFUs) observed within hours at effective concentrations .
Efficacy in Clinical Applications
This compound is widely used for treating various fungal infections, particularly oral candidiasis and cutaneous candidiasis. Its formulations include suspensions and pastilles, each demonstrating varying degrees of efficacy.
Clinical Studies Overview
- Oral Candidiasis : A systematic review indicated that this compound pastilles were significantly more effective than placebo for denture stomatitis. However, this compound suspension showed inferior efficacy compared to fluconazole in treating oral candidiasis in vulnerable populations such as infants and HIV/AIDS patients .
- Cutaneous Candidiasis : Historical studies have shown this compound ointment to be effective against skin lesions caused by Candida, with significant clinical response rates compared to placebo .
Efficacy Data Table
| Formulation | Condition | Efficacy (%) | Comparison Drug |
|---|---|---|---|
| This compound Pastille | Denture Stomatitis | 79.6% - 87.5% | Placebo |
| This compound Suspension | Oral Candidiasis | 9% - 63.5% | Fluconazole |
| This compound Ointment | Cutaneous Candidiasis | 78% (clearing rate) | Placebo |
Safety Profile
This compound is generally considered safe with minimal systemic absorption when administered orally or topically. Common adverse effects include gastrointestinal disturbances and a poor taste associated with oral formulations . Notably, high concentrations can lead to cytotoxicity in mammalian cells; however, formulations like this compound-Intralipid have shown reduced toxicity while maintaining antifungal activity .
Case Studies
Several case studies illustrate the effectiveness of this compound in treating specific patient populations:
- Infants with Oral Thrush : In cases involving infants with oral thrush, this compound was administered as a swish-and-swallow treatment, showing significant clinical improvements by day four post-treatment .
- Cancer Patients : A study involving cancer patients demonstrated a clinical cure rate of 87.5% when using a combination of this compound suspension and pastilles for oral candidiasis .
属性
IUPAC Name |
(1S,3R,4R,7R,9R,11R,15S,16R,17R,18S,19E,21E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(2R,3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-1,3,4,7,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,25,27,29,31-hexaene-36-carboxylic acid |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C47H75NO17/c1-27-17-15-13-11-9-7-5-6-8-10-12-14-16-18-34(64-46-44(58)41(48)43(57)30(4)63-46)24-38-40(45(59)60)37(54)26-47(61,65-38)25-36(53)35(52)20-19-31(49)21-32(50)22-33(51)23-39(55)62-29(3)28(2)42(27)56/h5-6,8,10-18,27-38,40-44,46,49-54,56-58,61H,7,9,19-26,48H2,1-4H3,(H,59,60)/b6-5+,10-8+,13-11+,14-12+,17-15+,18-16+/t27-,28-,29-,30+,31+,32+,33+,34-,35+,36+,37-,38-,40+,41-,42+,43+,44-,46-,47+/m0/s1 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
VQOXZBDYSJBXMA-NQTDYLQESA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CC1C=CC=CCCC=CC=CC=CC=CC(CC2C(C(CC(O2)(CC(C(CCC(CC(CC(CC(=O)OC(C(C1O)C)C)O)O)O)O)O)O)O)C(=O)O)OC3C(C(C(C(O3)C)O)N)O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Isomeric SMILES |
C[C@H]1/C=C/C=C/CC/C=C/C=C/C=C/C=C/[C@@H](C[C@H]2[C@@H]([C@H](C[C@](O2)(C[C@H]([C@@H](CC[C@H](C[C@H](C[C@H](CC(=O)O[C@H]([C@@H]([C@@H]1O)C)C)O)O)O)O)O)O)O)C(=O)O)O[C@H]3[C@H]([C@H]([C@@H]([C@H](O3)C)O)N)O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C47H75NO17 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID80872323 |
Source
|
| Record name | (7R,10R)-8,9-Dideoxy-28,29-dihydro-7,10-dihydroxyamphotericin B | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID80872323 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
926.1 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Solubility |
MW: 926.12 /Form not specified/, Mg/ml at about 28 °C: methanol 11.2, ethanol 1.2, chloroform 0.48, carbon tetrachloride 1.23, benzene 0.28, toluene 0.285, acetone 0.390, ethyl acetate 0.75, ethylene glycol 8.75, Insol in ether, In water, 3.60X10+2 mg/L at 24 °C |
Source
|
| Record name | NYSTATIN | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3138 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
Mechanism of Action |
Nystatin exerts its antifungal activity by binding to sterols in the fungal cell membrane. The drug is not active against organisms (e.g., bacteria) that do not contain sterols in their cell membrane. As a result of this binding, the membrane is no longer able to function as a selective barrier, and potassium and other cellular constituents are lost., ... /Antimicrobial/ agents that act directly on the cell membrane of the microorganism, affecting permeability and leading to leakage of intracellular compounds; these include ... the polyene antifungal agents nystatin ... which bind to cell-wall sterols ... |
Source
|
| Record name | NYSTATIN | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3138 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
Color/Form |
Light yellow powder, Yellow to tan powder | |
CAS No. |
34786-70-4, 1400-61-9 |
Source
|
| Record name | Nystatin A1 | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=34786-70-4 | |
| Description | CAS Common Chemistry is an open community resource for accessing chemical information. Nearly 500,000 chemical substances from CAS REGISTRY cover areas of community interest, including common and frequently regulated chemicals, and those relevant to high school and undergraduate chemistry classes. This chemical information, curated by our expert scientists, is provided in alignment with our mission as a division of the American Chemical Society. | |
| Explanation | The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated. | |
| Record name | Nystatin A1 | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0034786704 | |
| Description | ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system. | |
| Record name | (7R,10R)-8,9-Dideoxy-28,29-dihydro-7,10-dihydroxyamphotericin B | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID80872323 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | Nystatin | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.014.317 | |
| Description | The European Chemicals Agency (ECHA) is an agency of the European Union which is the driving force among regulatory authorities in implementing the EU's groundbreaking chemicals legislation for the benefit of human health and the environment as well as for innovation and competitiveness. | |
| Explanation | Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page. | |
| Record name | NYSTATIN A1 | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/W1LX4T91WI | |
| Description | The FDA Global Substance Registration System (GSRS) enables the efficient and accurate exchange of information on what substances are in regulated products. Instead of relying on names, which vary across regulatory domains, countries, and regions, the GSRS knowledge base makes it possible for substances to be defined by standardized, scientific descriptions. | |
| Explanation | Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required. | |
| Record name | NYSTATIN | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3138 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
Melting Point |
Gradually decomp above 160 °C without melting by 250 °C |
Source
|
| Record name | NYSTATIN | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3138 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
Retrosynthesis Analysis
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Strategy Settings
| Precursor scoring | Relevance Heuristic |
|---|---|
| Min. plausibility | 0.01 |
| Model | Template_relevance |
| Template Set | Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis |
| Top-N result to add to graph | 6 |
Feasible Synthetic Routes
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