Discovery of novel indole and indoline derivatives against Candida albicans as potent antifungal agents

Jia Ma; Yuan Jiang; Xinying Zhuang; Huiting Chen; Yunhong Shen; Zewei Mao; Gaoxiong Rao; Ruirui Wang

doi:10.1016/j.bmcl.2022.128826

Discovery of novel indole and indoline derivatives against Candida albicans as potent antifungal agents

Bioorg Med Chem Lett. 2022 Sep 1:71:128826. doi: 10.1016/j.bmcl.2022.128826. Epub 2022 May 31.

Authors

Jia Ma¹, Yuan Jiang², Xinying Zhuang², Huiting Chen³, Yunhong Shen², Zewei Mao⁴, Gaoxiong Rao⁵, Ruirui Wang⁶

Affiliations

¹ College of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, PR China; College of Pharmacy, Dali University, Dali 671000, PR China.
² College of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, PR China.
³ College of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, PR China; Engineering Laboratory for National Health Theory and Product of Yunnan Province, Yunnan University of Chinese Medicine, Kunming 650500, PR China.
⁴ College of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, PR China; Engineering Laboratory for National Health Theory and Product of Yunnan Province, Yunnan University of Chinese Medicine, Kunming 650500, PR China. Electronic address: maozw@ynutcm.edu.cn.
⁵ College of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, PR China; Engineering Laboratory for National Health Theory and Product of Yunnan Province, Yunnan University of Chinese Medicine, Kunming 650500, PR China. Electronic address: Rao_gx@163.com.
⁶ College of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, PR China; Engineering Laboratory for National Health Theory and Product of Yunnan Province, Yunnan University of Chinese Medicine, Kunming 650500, PR China; College of Pharmacy, Dali University, Dali 671000, PR China. Electronic address: wangrryucm@126.com.

PMID: 35661686
DOI: 10.1016/j.bmcl.2022.128826

Abstract

With the widespread use of azole antifungals in the clinic, the drug resistance has been emerging continuously. In this work, we have designed and prepared a series of novel indole and indoline derivatives, and in vitro antifungal activity against C. albicans were evaluated. The results showed that title compounds exhibited good antifungal effect on Azole-resistant C. albicans. Further mechanism study demonstrated that S18 could inhibit the biofilm formation and hyphae growth of C. albicans through the Ras-cAMP-PKA signaling pathway.

Keywords: Antifungal activity; Indole; Indoline; Ras-cAMP-PKA pathway.

Publication types

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

MeSH terms

Antifungal Agents* / pharmacology
Azoles / pharmacology
Biofilms
Candida albicans*
Indoles / pharmacology
Microbial Sensitivity Tests

Substances

Antifungal Agents
Azoles
Indoles
indoline