Synergistic activity of the combination of falcarindiol and itraconazole in vitro against dermatophytes

Siyue Kan; Jingwen Tan; Qing Cai; Lulu An; Zhiqin Gao; Hong Yang; Siyu Liu; Risong Na; Lianjuan Yang

doi:10.3389/fcimb.2023.1128000

Synergistic activity of the combination of falcarindiol and itraconazole in vitro against dermatophytes

Front Cell Infect Microbiol. 2023 May 3:13:1128000. doi: 10.3389/fcimb.2023.1128000. eCollection 2023.

Authors

Siyue Kan¹, Jingwen Tan¹, Qing Cai¹, Lulu An¹, Zhiqin Gao¹, Hong Yang¹, Siyu Liu¹, Risong Na², Lianjuan Yang¹

Affiliations

¹ Department of Medical Mycology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.
² College of Plant Protection, Henan Agricultural University, Zhengzhou, China.

Abstract

Previous studies have shown that natural polyacetylene alcohols, such as falcarindiol (FADOH), have good antifungal effects on plant fungi. While its effect on fungi that infect humans remains to be explored. In our study, checkerboard microdilution, drop-plate assay, and time-growth method were employed to analyze the interactions between FADOH and itraconazole (ITC) in vitro against dermatophytes, including 12 Trichophyton rubrum (T. rubrum), 12 Trichophyton mentagrophytes (T. mentagrophytes), and 6 Microsporum canis (M. canis). The results showed that the combination of FADOH and ITC exhibited synergistic and additive activity against 86.7% of all tested dermatophytes. FADOH had an excellent synergistic effect on ITC against T. rubrum and T. mentagrophytes; the synergistic rates were 66.7% and 58.3%, respectively. On the contrary, FADOH combined with ITC showed poor synergistic inhibitory activity (16.7%) against M. canis. Moreover, the additive rates of these two drugs against T. rubrum, T. mentagrophytes, and M. canis were 25%, 41.7%, and 33.3%, respectively. No antagonistic interactions were observed. The drop-plate assay and time-growth curves confirmed that the combination of FADOH and ITC had a potent synergistic antifungal effect. The in vitro synergistic effect of FADOH and ITC against dermatophytes is reported here for the first time. Our findings suggest the potential use of FADOH as an effective antifungal drug in the combined therapy of dermatophytoses caused especially by T. rubrum and T. mentagrophytes.

Keywords: additive; dermatophytes; falcarindiol; itraconazole; polyacetylene alcohols; synergistic.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antifungal Agents / pharmacology
Arthrodermataceae*
Humans
Itraconazole* / pharmacology
Microbial Sensitivity Tests
Trichophyton

Substances

Itraconazole
Antifungal Agents
falcarindiol

Supplementary concepts

Trichophyton rubrum
Microsporum canis

Grants and funding

This work was supported by the National Natural Science Foundation of China (Grant No. 82173429 to LY), the Science and Technology Commission of Shanghai Municipality (Grant No. 21Y11904900 to LY) and the Clinical Research and Cultivation Project of Shanghai Skin Disease Hospital (Grant No. lcfy2022-05 to SK).