All about polyenes

Pharmacology is a wide rooted branch of medicine. It mainly deals with medicine, its formulation, composition, usage, dosage, effects, toxicity studies and more drug-related analyses. The drugs are used in the treatment of various kinds of ailments and diseases of diverse origins. The common classification of drugs is based on their specificity against a particular microorganism. A drug that inhibits the growth, development and reproduction of fungal species are called antifungal agents. Polyenes make up a huge number of antifungal agents. Polyenes are a type of hydrocarbons that have a strong impact on fungi. They are of various types and possess different mechanisms of action against fungi. In this article, you will learn more about polyenes, the classification of antifungal agents, polyene antibiotics and antifungal mechanisms of action.

Classification of antifungal agents

The Classification of Antifungal agents is described below:

• Polyenes: They are hydrocarbons useful in the treatment of fungal diseases. It includes Nystatin and Natamycin.
• Imidazole: They are crystalline organic compounds that consist of an aromatic five-membered ring. It includes ketoconazole and miconazole. 
• Triazole: It is composed of two carbon atoms and three nitrogen atoms. It includes fluconazole and itraconazole. 
• Allylamines: It is a strong basic organic compound. It is widely used in the production of mercurial diuretics. It includes Naftifine and terbinafine. 
• β-D-Glucan Synthase Inhibitors: It inhibits the cell wall of microbes. It includes echinocandins and caspofungin. 
• Other drugs like griseofulvin, flucytosine and tolnaftate fall under antifungal drugs. 

Polyene antibiotics

Polyenes are commonly and widely applied antifungal chemicals or drugs. They are composed of a cyclic amphiphilic macrolide substructure. They have a broad spectrum of activity that can act against a wide variety of organisms. The carbon bonds are single or double in number. They are poly-unsaturated compounds. Polyene antibiotics possess high activity against microbes, specifically fungi. The most common producer of polyene antibiotics in Streptomyces species. These drugs react with the cell membranes of fungi, they combine with sterols of the cells of fungi resulting in the leakage of cell matter by forming channels across the membrane. 

Examples of polyene antibiotics that serve as antifungal agents are as follows:

• Nystatin
• Candicidin
• Amphotericin B
• Trichomycin
• Pimaricin
• Natamycin

Antifungal mechanism of action

The antifungal mechanism of action of polyenes is that they attach themselves to the ergosterol of the fungal cell membrane. Ergosterol is a type of organic compound that consists of a steroid and an alcohol group found attached to the cell wall of fungi. It then produces aqueous pores on the walls of fungal cells. This results in the leakage of intracellular ions out of the cells which drastically affects the active transport processes that depend on membrane potential. They exhibit two modes of action. One is fungicidal, where the fungi are destroyed or killed. The other is fungistatic, where the fungal activity and spread are mitigated. 

Amphotericin B

It is a chief antifungal antibiotic that is commonly employed against mycosis. It exhibits a broad spectrum of activity against a wide range of fungi that includes Candida species, Aspergillus species,  Cryptococcus neoformans and the zygomycetes. It can also treat dimorphic fungi that can give rise to free-living vegetative cells like Histoplasma capsulatum, Coccidioides immitis, Paracoccidioides brasiliensis and Blastomyces dermatitidis. The drug is administered intravenously and it is also found to exhibit some side effects on our body. It has a wide range of curative properties against diseases like invasive and mucosal Candidiasis, Phaeohyphomycosis, Blastomycosis, Aspergillosis, Coccidioidomycosis, Penicilliosis, Cryptococcosis, Mucormycosis, Histoplasmosis and Sporotrichosis.

Nystatin

Nystatin is a highly active antifungal drug. It was first isolated and derived from Streptomyces noursei during research in 1949. It is highly effective against Candida species and exhibits moderate effect against Aspergillus species. It is taken as oral medicine or as external medicine as lotions and ointments. Nystatin forms aggregates that are highly toxic. It exhibits toxicity both externally and internally. Commercially available nystatin is formulated and sold in less toxic forms. 

Natamycin

Natamycin can be popularly referred to as natacyn and pimaricin. It is naturally produced by the fermentation of Streptomyces natalensis. It can exhibit a high antifungal mechanism of action in lower concentrations of the drugs. It is less soluble in water and the minimum 

inhibitory concentration is less than 10ppm. It exhibits high effectiveness against Aspergillus species and Fusarium species. It blocks the ergosterol of the fungal cell wall and inhibits its growth and activity. It is used to treat fungal keratitis and corneal infections caused by Aspergillus species and Fusarium species.

Conclusion

Antifungal agents are widely isolated, produced and marketed for the treatment of a wide range of fungal infections. Polyenes being widely used in the form of polyene antibiotics are produced in a vast range as an effective drug for treatment. Research is being conducted with polyenes and other antifungal agents to produce high specificity, a broad range of treatments, reduce toxicity, develop pharmacokinetic profiles, bioavailability and enhance reactivity.