New aminopiperidine-azoles as antifungal agents against Candida albicans with mechanistic insights into the cAMP-PKA pathway

  • Bioorg Med Chem Lett. 2026 Oct:139:130714. doi: 10.1016/j.bmcl.2026.130714.
Rui Guo  1 ,  Yingliang Wei  1 ,  Ting Yao  1 ,  Ruirui Wang  1 ,  Qin Li  2 ,  Chunyan Hu  3
Affiliations
  • 1. Yunnan University of Chinese Medicine, Kunming 650500, PR China.
  • 2. Yunnan University of Chinese Medicine, Kunming 650500, PR China. Electronic address: [email protected].
  • 3. Yunnan University of Chinese Medicine, Kunming 650500, PR China. Electronic address: [email protected].
PMID: 42341851 DOI: 10.1016/j.bmcl.2026.130714
Abstract

Candida albicans infections are becoming increasingly prevalent, making the development of new drugs an urgent priority. In this study, a series of new aminopiperidine-azole derivatives were designed, synthesized, and evaluated for their in vitro Antifungal activity against both FLC-sensitive and -resistant strains of C. albicans. Several compounds exhibited good Antifungal activity, with compound 5p demonstrating the most promising efficacy against the sensitive strain SC5314 (MIC50 = 0.28 μM). Mechanism studies revealed that 5p significantly inhibited biofilm formation and hyphal growth by downregulating key genes of the cAMP-PKA signaling pathway, including RAS1, EFG1, BCR1, ECE1, and HWP1. Furthermore, 5p showed low cytotoxicity against human bronchial epithelial cells (16HBE) at effective concentrations. These findings suggest that 5p is a promising lead compound for the development of new Antifungal drugs.

Keywords
Aminopiperidine-azoles; Antifungal activity; Mechanism; cAMP-PKA pathway.
Products