New Conjugates of Polyene Macrolide Amphotericin B with Benzoxaboroles: Synthesis and Properties

Overview

Journal J Antibiot (Tokyo)

Specialties Infectious Diseases
Pharmacology

Date 2016 Mar 24

PMID 27005557

Citations 6

Authors

Anna N Tevyashova

Alexander M Korolev

Aleksey S Trenin

Lyubov G Dezhenkova

Alexander A Shtil

Vladimir I Polshakov

Oleg Yu Savelyev

Evgenia N Olsufyeva

Affiliations

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Abstract

A novel series of conjugates of the antifungal antibiotic amphotericin B (AmB) with benzoxaboroles was synthesized. Antifungal activity of new compounds was tested on yeastβ Candida albicans and Cryptococcus humicolus and filamentous fungi Aspergillus niger and Fusarium oxysporum using the broth microdilution method. The potency of di-modified derivatives against the tested strains was similar to that of the parent AmB. New derivatives demonstrated differential toxicity against human cells (colon epithelium or red blood cells). The di-modified conjugate 2-(N,N-dimethylamino)ethylamide of 3'-N-[3-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-7-yl)propanoyl] AmB (9) showed the best combination of a high antifungal activity with a low cytotoxic and hemolytic potency.

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References

Rock F, Mao W, Yaremchuk A, Tukalo M, Crepin T, Zhou H . An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site. Science. 2007; 316(5832):1759-61. DOI: 10.1126/science.1142189. View

Dembitsky V, Al Quntar A, Srebnik M . Natural and synthetic small boron-containing molecules as potential inhibitors of bacterial and fungal quorum sensing. Chem Rev. 2010; 111(1):209-37. DOI: 10.1021/cr100093b. View

Qiao Z, Wang Q, Zhang F, Wang Z, Bowling T, Nare B . Chalcone-benzoxaborole hybrid molecules as potent antitrypanosomal agents. J Med Chem. 2012; 55(7):3553-7. DOI: 10.1021/jm2012408. View

Delaglio F, Grzesiek S, Vuister G, Zhu G, Pfeifer J, Bax A . NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J Biomol NMR. 1995; 6(3):277-93. DOI: 10.1007/BF00197809. View

Baker S, Zhang Y, Akama T, Lau A, Zhou H, Hernandez V . Discovery of a new boron-containing antifungal agent, 5-fluoro-1,3-dihydro-1-hydroxy-2,1- benzoxaborole (AN2690), for the potential treatment of onychomycosis. J Med Chem. 2006; 49(15):4447-50. DOI: 10.1021/jm0603724. View

Printsevskaya S, Reznikova M, Korolev A, Lapa G, Olsufyeva E, Preobrazhenskaya M . Synthesis and study of antibacterial activities of antibacterial glycopeptide antibiotics conjugated with benzoxaboroles. Future Med Chem. 2013; 5(6):641-52. DOI: 10.4155/fmc.13.16. View

Tevyashova A, Olsufyeva E, Solovieva S, Printsevskaya S, Reznikova M, Trenin A . Structure-antifungal activity relationships of polyene antibiotics of the amphotericin B group. Antimicrob Agents Chemother. 2013; 57(8):3815-22. PMC: 3719701. DOI: 10.1128/AAC.00270-13. View

Mahalingam A, Geonnotti A, Balzarini J, Kiser P . Activity and safety of synthetic lectins based on benzoboroxole-functionalized polymers for inhibition of HIV entry. Mol Pharm. 2011; 8(6):2465-75. PMC: 3445258. DOI: 10.1021/mp2002957. View

Adamczyk-Wozniak A, Borys K, Sporzynski A . Recent developments in the chemistry and biological applications of benzoxaboroles. Chem Rev. 2015; 115(11):5224-47. DOI: 10.1021/cr500642d. View

10.

Preobrazhenskaya M, Olsufyeva E, Tevyashova A, Printsevskaya S, Solovieva S, Reznikova M . Synthesis and study of the antifungal activity of new mono- and disubstituted derivatives of a genetically engineered polyene antibiotic 28,29-didehydronystatin A1 (S44HP). J Antibiot (Tokyo). 2009; 63(2):55-64. DOI: 10.1038/ja.2009.118. View

11.

Preobrazhenskaya M, Olsufyeva E, Solovieva S, Tevyashova A, Reznikova M, Luzikov Y . Chemical modification and biological evaluation of new semisynthetic derivatives of 28,29-Didehydronystatin A1 (S44HP), a genetically engineered antifungal polyene macrolide antibiotic. J Med Chem. 2008; 52(1):189-96. DOI: 10.1021/jm800695k. View

12.

Baker S, Tomsho J, Benkovic S . Boron-containing inhibitors of synthetases. Chem Soc Rev. 2011; 40(8):4279-85. DOI: 10.1039/c0cs00131g. View

13.

Volpon L, Lancelin J . Solution NMR structure of five representative glycosylated polyene macrolide antibiotics with a sterol-dependent antifungal activity. Eur J Biochem. 2002; 269(18):4533-41. DOI: 10.1046/j.1432-1033.2002.03147.x. View