Амфотерицин А

Description

Amphotericin A is a polyene macrolide antibiotic, a waste product of the soil bacterium Streptomyces nodosus, a saturated structural analogue of amphotericin B. It belongs to the class of lactones. Structurally identical to amphotericin B, with the exception of one bond between 28 and 29 carbon atoms of the macrolactone cycle: in amphotericin A this bond is single (saturated), in amphotericin B it is double.

Basic Attributes

• CAS No.: 1405-32-9
• Chemical formula: C47H75NO17
• Molecular weight: 924.127
• Exact weight: 926.09
• UNII: 6KQ75HL677
• PSA Specifications: 320
• XLogP3: -0.2

Synonyms

Amphotericin B, 28,29-dihydro-; 14,39-dioxabicyclo[33,3,1]nonatriacontane, a derivative of amphotericin B; 28,29-dihydroamphotericin B; alternative CAS number 37187-24-9.

Mechanism of action

Like amphotericin B, it binds to ergosterol in the fungal cell membrane, forms pores and increases membrane permeability, which leads to leakage of intracellular contents and cell death. The absence of one double bond in the polyene chain reduces the binding affinity for ergosterol compared to amphotericin B, which is why the therapeutic efficacy of amphotericin A is lower.

Scope of application

Due to its lower activity compared to amphotericin B, the compound is not used as an independent clinical drug. The main area of ​​application is structure-activity studies of polyene antibiotics: comparison of saturated (amphotericin A) and unsaturated (amphotericin B) analogues allows us to understand the contribution of a specific double bond of the macrolactone ring to the membranotropic mechanism of action. The compound is also used in studying the mechanisms of resistance to antifungal drugs and in the development of synthetic derivatives with an improved therapeutic profile and reduced toxicity.

Place among polyene antibiotics

Polyene macrolides (amphotericin A and B, nystatin, natamycin) share a common principle of action - binding to membrane sterols and the formation of ion channels. Amphotericin A is present as a minor accompanying component in fermentation preparations of Streptomyces nodosus along with the main product amphotericin B and is used as a reference compound when monitoring the composition of technical batches of the antibiotic.

Toxicity and safety precautions

A separate acute toxicity profile for amphotericin A has not been found in open sources; When working with polyene antibiotics of this series, they are based on the common risk for the class of irritation of the respiratory tract and mucous membranes when inhaling dust.

Storage and handling

The polyene structure is photosensitive and prone to oxidation of conjugated double bonds. Store in an airtight container, protected from light, in the refrigerator or freezer, minimize contact with air and avoid overheating. Work with dry powder with gloves, prepare solutions immediately before use. The product is intended for laboratory and research use.

Implications for quality control

Since amphotericin A accompanies amphotericin B in fermentation batches of Streptomyces nodosus, determination of its content is included in the quality control specification of the technical substance of the antibiotic: an excessive proportion of the saturated analogue reduces the total antifungal activity of the drug and requires adjustment of fermentation conditions or additional purification.