The Hydrophobicity and Antifungal Potentiation of Burkholdine Analogues

Hiroyuki Konno; Mio Sasaki; Hinata Sano; Keima Osawa; Kazuto Nosaka; Shigekazu Yano

doi:10.3390/molecules27041191

The Hydrophobicity and Antifungal Potentiation of Burkholdine Analogues

Molecules. 2022 Feb 10;27(4):1191. doi: 10.3390/molecules27041191.

Authors

Hiroyuki Konno¹, Mio Sasaki¹, Hinata Sano¹, Keima Osawa¹, Kazuto Nosaka², Shigekazu Yano¹

Affiliations

¹ Department of Biological Engineering, Graduate School of Science and Engineering, Yamagata University, Yonezawa 992-8510, Japan.
² Faculty of Pharmaceutical Science, Mukogawa Women's University, Nishinomiya 663-8179, Japan.

Abstract

The burkholdines are a family of cyclic lipopeptides reported to exhibit antifungal activity. We synthesized a series of 18 burkholdine analogues in good yield by conventional Fmoc-SPPS followed by cyclization with DIPCI/HOBt in the solution phase. Although none of the synthesized peptides exhibited antifungal activity, several did potentiate the antibiotic effect of the antibiotic G418, including the Thr-bearing Bk analogue (4b) and the tartaramide-bearing Bk analogue (5b). This work exemplifies the potential of burkholdine analogues as potentiating agents.

Keywords: antifungal activity; burkholdine; cyclic octalipopeptide; potentiation effect.

MeSH terms

Antifungal Agents / chemistry*
Antifungal Agents / pharmacology
Hydrophobic and Hydrophilic Interactions
Lipopeptides / chemistry*
Lipopeptides / pharmacology

Substances

Antifungal Agents
Lipopeptides
burkholdine