Amphotericin B

Base Information

• Chemical Name: Amphotericin B
• CAS No.: 1397-89-3
• Molecular Formula: C47H73NO17
• Molecular Weight: 924.093
• Hs Code.: 29419090
• Mol file: 1397-89-3.mol

Synonyms:Fungizone;Amphozone;component of Mysteclin-F;Mysteclin-F;33-((3-amino-3,6-dideoxyhexopyranosyl)oxy)-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid;Amphocin;IAB;Amphotericin B (JP14/USP);Amphotericin B (U.S. FDA Approved);AmphotericcinB;

Chemical Property of Amphotericin B

Chemical Property:

• Appearance/Colour: crystalline yellow solid
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: >170 °C
• Refractive Index: 1.614
• Boiling Point: 1140.4 °C at 760 mmHg
• PKA: pKa ～5.7(DMF/H2O) (Uncertain)
• Flash Point: 643.5 °C
• PSA: 319.61000
• Density: 1.34 g/cm³
• LogP: 1.41200
• Storage Temp.: 2-8°C
• Sensitive.: Moisture & Light Sensitive
• Solubility.: sterile water: 20 mg/mL as a stock solution. Stock solution
• Water Solubility.: <0.1 g/100 mL at 21℃

Purity/Quality:

99.9% ^*data from raw suppliers

Amphotericin B, USP ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: C,Xi,Xn,T
• Statements: 36/37/38-22-40-23/24/25
• Safety Statements: 26-36/37/39-45-36-60-37

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Indications: Treatment of visceral and mucocutaneous leishmaniasis unresponsive to standard drugs (pentavalent antimonials and pentamidine). Amphotericin B (Fungizone) is an amphoteric polyene macrolide produced by Streptomyces nodosus. It exerts its antifungal activity principally by binding to sterols in the fungal cell membrane, resulting in loss of membrane-selective permeability, leakage, and subsequent cell death. It is used topically in the treatment of superficial C. albicans infection and is orally active against Aspergillus, Coccidioides, Cryptococcus, Exophilia, histoplasmosis, Mucor, Paracoccidioides, and Rhodotorula. It is also active against many strains of Leishmania, Naegleria, and Acanthamoeba. Fusarium, Pseudallescheria, and Scedosporium are generally resistant to amphotericin B. It is fungistatic or fungicidal, depending on the concentration used and the fungal susceptibility. It is ineffective against dermatophytes. The drug is yellow orange, odorless, and may stain skin. Adverse reactions with topical administration are limited. When administered by IV, amphotericin B may be associated with infusion reactions, nephrotoxicity, anemia, gastrointestinal distress, hepatitis, and neurologic effects. Amphotericin B is the first-choice drug for treating deep fungus infection with a broad antifungal spectrum. It has inhibitory effect on cryptococcus, coccidioidomyces immitis, candida albicans, and blastomyces with exhibiting bactericidal effect at high concentration, and therefore is a kind of drugs being effective in treating deep fungus infection. Major clinical indications are as follows: 1. It can be used for the treatment of cryptococcosis, North American blastomycosis, disseminated candidiasis, coccidioidomycosis, and histoplasmosis. 2. It can be used for the treatment of mucormycosis caused by the rhizopus genera, absidia, endomycopsis and the basidiobulus sp. 3. It can be used for the treatment of sporotrichum disease caused by schenker sporotrichosis. 4. It can be used for the treatment of aspergillosis caused by the Aspergillus fumigatus. 5. External preparation is suitable for treating chromomycosis, fungal infections infection after burning, respiratory tract candida, Aspergillus or cryptococcus infection, and fungal corneal ulcer. Amphotericin B (Fungizone), a polyene antifungal drug produced by the actinomycete Streptomyces nodosus, consists of a large ring structure with both hydrophilic and lipophilic regions. Polyene antifungal drugs bind to the fungal cell membrane component ergosterol, leading to increased fungal cell membrane permeability and the loss of intracellular constituents. Amphotericin has a lesser affinity for the mammalian cell membrane component cholesterol, but this interaction does account for most adverse toxic effects associated with this drug.
• Drug interactions: 1, Adrenal cortical hormone, such drugs can be used in combination for controlling the adverse reactions of amphotericin B, but it is generally not recommended to applied both drugs at the same time for that it can amplify the symptoms of amphotericin B induced hypokalemia. If it is necessary to apply them at the same time, it is recommended to apply adrenal cortical hormone at its minimum dose and with the shortest period of treatment. Moreover, monitoring the potassium concentration and heart function of the patients is also demanded. 2, Digitalis glycosides, hypokalemia caused by this product can strengthen potential digitalis toxicity. Simultaneous application should subject to the close monitor of the blood potassium concentration and heart function. 3, Fluorine cytosine has synergetic effect with amphotericin B, but this product can increase the intake of the former one and do harm to it excretion through renal, and thus further amplifying the toxic effects of fluoride cytosine. 4. This product has antagonist effect in vitro with pyrrole antifungal drugs such as ketoconazolen, fluconazole and itraconazole. 5, Nephrotoxicity drugs such as aminoglycoside, antitumor drugs, capreomycin, polymyxin class and vancomycin can have their nephrotoxicity enhanced when used in combination with this drug. 6, Bone marrow inhibitor and radiotherapy can aggravate the anemia o patients, and therefore should be applied with reduced amount when used in combination with amphotericin B. 7, the hypokalemia induced by this product can strengthen the effect of neuromuscular blockers. Therefore, the monitor of potassium concentration is demanded when these two kinds of drugs are used in combination. 8, application of urine alkaline medicine can enhance the excretion of this product and prevent or reduce of possibility of the occurrence o renal tubular acidosis.
• Uses: 1. The product has strong inhibitory effect on various kinds of fungal infection, such as Cryptococcus neoformans, dermatitis budding yeast, histoplasma capsulatum, sporothrix schenkii, white candida, mucor sp and Coccidioides immitis. The goods are the primary choice of drugs for treating deep fungal disease. 2. It is a kind of polyene antifungal drugs. This drug binds to the sterol located on the fungal cell membranes sterol, disrupting the membrane permeability, causing the leakage of bacteria intracellular potassium ion, nucleotides, amino acids and therefore playing bactericidal effect by disrupting the normal metabolism. Polypeptide antibiotic active against gram positive bacteria. Antifungal. Amphotericin B is heptaene polyene antifungal originally discovered as a metabolite of Streptomyces nodosus in 1956. Amphotericin B acts by binding sterols in the cell membrane leading to the formation of transmembrane channels and subsequent ion leakage. Amphotericin B is poorly water soluble so has been developed for therapeutic use as a complex with desoxylate or in liposomes to improve bioavailability. Amphotericin B is widely used as a research reagent in diverse applications with over 15,000 literature citations. Amphotericin B (Funizone) is an antifungal macrolide antibiotic produced by Streptomyces nodosus that has been used as an alternative, albeit more toxic, drug to the antimonials. See also Amebiasis (Amebic Dysentery) . It acts as a leishmanicide against the visceral and mucocutaneous forms of the disease. To overcome its potentially severe nephrotoxicity, the drug must be administered over an extended period of time.
• Description: Amphotericin B (1397-89-3) is a powerful antimycotic, effective against a wide variety of fungi, including yeast, via two mechanisms: forming pores in the plasma membrane, leading to leakage and death1, and causing oxidative stress2. Other mechanisms have more recently been proposed, including formation of intracellular amphotericin B-containing vesicular bodies that target vacuoles.3 Amphotericin B is also effective against some parasites, such as Leishmania spp.4 Because of its potency and broad-spectrum activity, it is a common additive used to maintain sterility in cell culture and viral transport media.
• Therapeutic Function: Antifungal
• Clinical Use: Aspergillosis Systemic mycoses with dimorphic fungi (blastomycosis, coccidioidomycosis, histoplasmosis, paracoccidioidomycosis, penicilliosis) Candidosis Cryptococcosis Hyalohyphomycosis, mucormycosis, phaeohyphomycosis Visceral leishmaniasis Amphotericin B is most commonly used to treat serious disseminated yeast and dimorphic fungal infections in immunocompromised hospitalized patients. As additional experience has been gained in the treatment of fungal infections with the newer azoles, the use of amphotericin B has diminished; if azole drugs have equivalent efficacy, they are preferred to amphotericin B because of their reduced toxicity profile and ease of administration. For the unstable neutropenic patient with Candida albicans fungemia, amphotericin B is the drug of choice. Amphotericin B remains the drug of choice in the treatment of invasive aspergillosis, locally invasive mucormycosis, and many disseminated fungal infections occurring in immunocompromised hosts (the patient population most at risk for serious fungal infections). For example, the febrile neutropenic oncology patient with persistent fever despite empirical antibacterial therapy is best treated with amphotericin B for possible Candida spp. sepsis.

Technology Process of Amphotericin B

There total 13 articles about Amphotericin B which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 80.0%

amphotericin B methyl ester (36148-89-7) → AmBisome (1397-89-3)

Guidance literature:

With lithium hydroxide; In tetrahydrofuran; water; at 25 ℃; for 1h;

DOI:10.1021/ja00243a043

Reference yield:

amphotericin B methyl pivalate (1112349-87-7) → AmBisome (1397-89-3)

Guidance literature:

With water; In dimethyl sulfoxide; at 37 ℃; pH=7; Phosphate buffer; Enzymatic reaction;

Reference yield:

C55H85NO17 → AmBisome (1397-89-3)

Guidance literature:

Multi-step reaction with 2 steps

1: 1.) CSA; 2.) H₂O / 1.) MeOH, 25 deg C, 2 h; 2.) MeOH, 25 deg C, 4 h

2: 80 percent / LiOH / tetrahydrofuran; H₂O / 1 h / 25 °C

With lithium hydroxide; camphor-10-sulfonic acid; water; In tetrahydrofuran; water;

DOI:10.1021/ja00243a043

upstream raw materials:

amphotericin B methyl ester

amphotericin B methyl pivalate

Downstream raw materials:

C₄₇H₇₃NO₁₇C₂H₂O

N-{N-[2-(4-methylpiperazin-1-yl)ethyl]succinimidyl}-amphotericin B

Refernces

• 1、 Sedlak, Milos,Pravda, Martin,Kubicova, Lenka,Mikulcikova, Petra,Ventura, Karel. "Synthesis and characterisation of a new pH-sensitive amphotericin B-poly(ethylene glycol)-b-poly(l-lysine) conjugate". . p. 2554 - 2557. Retrieved 2007.
• 2、 -. "POLYENE DIESTER ANTIBIOTICS". Page/Page column 20. . Retrieved 2010/08/22.