Polyene antimycotic

Short description: Class of antifungal compounds

Polyene antimycotics, sometimes referred to as polyene antibiotics, are a class of antimicrobial polyene compounds that target fungi.[1] These polyene antimycotics are typically obtained from certain species of Streptomyces bacteria. Previously, polyenes were thought to bind to ergosterol in the fungal cell membrane, weakening it and causing leakage of K+ and Na+ ions, which could contribute to fungal cell death. However, more detailed studies of polyene molecular properties have challenged this model suggesting that polyenes instead bind and extract ergosterol directly from the cellular membrane thus disrupting the many cellular functions ergosterols perform.[2][3] Amphotericin B, nystatin, and natamycin are examples of polyene antimycotics. They are a subgroup of macrolides.[4]

## Contents

* 1 Structures
* 2 Biosynthesis
* 3 Other examples of polyenes
* 4 References

## Structures

Their chemical structures feature a large ring of atoms (in essence, a cyclic ester ring) containing multiple conjugated carbon-carbon double bonds (hence polyene) on one side of the ring and multiple hydroxyl groups bonded to the other side of the ring. Their structures also often have a D-mycosamine (a type of amino-glycoside) group bonded to the molecule.[5] The series of conjugated double bonds typically absorbs strongly in the ultraviolet-visible region of the electromagnetic spectrum, often resulting in the polyene antibiotics having a yellow color.

Chemical structure of Amphotericin B. Amphotericin B is an example of a yellow polyene antimycotic agent. Note the alternating double and single bonds in the center and the mycosamine group in the bottom-right corner. Chemical structure of Nystatin. Chemical structure of Natamycin, sometimes called pimaricin.

## Biosynthesis

The natural route to synthesis includes polyketide synthase components.[6]

## Other examples of polyenes

* Rimocidin
* Filipin
* Candicin
* Hamycin
* Perimycin
* Dermostatin
* Turletricin

## References

1. ↑ Baron, S.; Dixon, D. M.; Walsh, T. J. (1996). "Antifungal Agents". Polyene Antifungal Drugs. The University of Texas Medical Branch at Galveston. ISBN 9780963117212. https://www.ncbi.nlm.nih.gov/books/NBK8263/. Retrieved 29 January 2010.
2. ↑ Thomas M, Anderson; Clay C, Mary; Cioffi G, Alexander; Diaz A, Katrina; Hisao S, Grant; Turrle D, Marcus; Nieuwkoop J, Andrew; Comellas, Gemma et al. (Mar 30, 2014). "Amphotericin forms an extramembranous and fungicidal sterol sponge". Nature Chemical Biology 10 (5): 400–406. doi:10.1038/nchembio.1496. PMID 24681535.
3. ↑ Robbins, Nicole; Caplan, Tavia; Cowen, Leah E. (September 8, 2017). "Molecular Evolution of Antifungal Drug Resistance". Annual Review of Microbiology 71: 753–775. doi:10.1146/annurev-micro-030117-020345. ISSN 1545-3251. PMID 28886681.
4. ↑ Hamilton-Miller (1973). "Chemistry and Biology of the Polyene Macrolide Antibiotics". Bacteriological Reviews (American Society for Microbiology) 37 (2): 166–196. doi:10.1128/BR.37.3.166-196.1973. PMID 4578757.
5. ↑ Volpon, Laurent; Lancelin, Jean-Marc (2002). "Solution NMR structure of five representative glycosylated polyene macrolide antibiotics with a sterol-dependent antifungal activity". European Journal of Biochemistry 269 (18): 4533–4541. doi:10.1046/j.1432-1033.2002.03147.x. PMID 12230565.
6. ↑ "A labile point in mutant amphotericin polyketide synthases". Biotechnol. Lett. 33 (6): 1121–6. Jan 26, 2011. doi:10.1007/s10529-011-0538-3. PMID 21267757. https://hal.archives-ouvertes.fr/hal-00663072/document.

* v
* t
* e

Antifungals (D01 and J02)

Wall/
membrane|

| Ergosterol
inhibitors|

| Azoles (lanosterol 14α-
demethylase inhibitors)|

| Imidazoles|

* Topical: bifonazole‡
* butoconazole
* chlormidazole‡
* clotrimazole#
* croconazole‡
* eberconazole
* econazole
* fenticonazole‡
* flutrimazole
* isoconazole
* ketoconazole
* luliconazole
* miconazole#
* neticonazole‡
* omoconazole‡
* oxiconazole
* sertaconazole
* sulconazole
* tioconazole

* Systemic: ketoconazole

|

Triazoles|

* Topical: efinaconazole
* fluconazole#
* terconazole

* Systemic: fluconazole#
* hexaconazole‡
* fosfluconazole
* isavuconazole
* itraconazole
* posaconazole
* voriconazole

* Unknown: albaconazole‡
* ravuconazole†

Thiazoles|

* Topical: abafungin‡

Polyene antimycotics
(ergosterol binding)|

* Topical: hamycin‡
* natamycin
* nystatin#
Systemic: amphotericin B#, hamycin‡

Squalene monooxygenase
inhibitors|

| Allylamines|

* Topical: naftifine
* terbinafine
Systemic: terbinafine

|

Benzylamines|

* Topical: butenafine

Others|

* Topical: amorolfine

β-glucan synthase
inhibitors|

* Systemic: echinocandins (anidulafungin
* biafungin
* caspofungin
* cilofungin
* micafungin)

Intracellular|

| Pyrimidine analogues/
thymidylate synthase inhibitors|

* Systemic: flucytosine#

|

Mitotic inhibitors|

* Systemic: griseofulvin#

Aminoacyl tRNA synthetase inhibitors|

* Topical: tavaborole

Others|

* bromochlorosalicylanilide
* chlorophetanol
* chlorphenesin
* ciclopirox
* crystal violet
* dimazole
* ethylparaben
* haloprogin‡
* polynoxylin
* potassium iodide#
* salicylic acid
* selenium disulfide#
* sodium thiosulfate#
* sulbentine
* taurolidine
* ticlatone
* tolciclate
* tolnaftate
* tribromometacresol
* undecylenic acid
* Whitfield's ointment#

* citronella oil
* lemon grass
* lemon myrtle
* orange oil
* patchouli
* tea tree oil
* PCP: atovaquone
* dapsone
* pentamidine

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

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