Ciclopirox Antifungal and Anti-Inflammatory Review: Dermatology to Oncology Original paper

What was reviewed?

This review explores the therapeutic potential of ciclopirox (CPX) and its ethanolamine salt ciclopirox olamine (CPO)—two hydroxypyridone antifungal agents with broad-spectrum antimicrobial, anti-inflammatory, and iron-chelating properties. The paper examines their established role in dermatology and investigates their emerging uses in oncology, virology, immunology, and neurology. The authors describe CPX/CPO’s unique mechanisms, structure–activity relationships, pharmacokinetics, and efficacy in diverse formulations including creams, shampoos, lacquers, and gels.

Who was reviewed?

The review draws on findings from in vitro studies, in vivo animal models, clinical trials, pharmacokinetic research, and microbial gene expression studies. It synthesizes data from both dermatological and non-dermatological disciplines, including microbiology, oncology, and virology, to contextualize CPX/CPO’s multifaceted utility.

Most important findings

Ciclopirox and its salt form, ciclopirox olamine, exhibit a unique mechanism of action that distinguishes them from conventional antifungals such as azoles and polyenes. Their primary mode involves intracellular iron chelation, targeting iron-dependent enzymes like ribonucleotide reductase and deoxyhypusine hydroxylase, thereby impairing fungal viability. Additionally, they disrupt mitochondrial function, energy metabolism, and membrane integrity, while also interfering with DNA repair, mitotic processes, and amino acid uptake.

Ciclopirox compounds exert potent anti-inflammatory effects by suppressing prostaglandins, leukotrienes, and pro-inflammatory cytokines including IL-1β, IL-6, and TNF-α. They are active against a wide spectrum of dermatophytes, Candida spp., Malassezia spp., Microsporum canis, and antibiotic-resistant bacteria, and demonstrate synergism with antifungal agents and mitochondrial electron transport chain (ETC) inhibitors. Notably, the review underscores microbiome-relevant implications, particularly in seborrheic dermatitis, where Malassezia dominance is accompanied by elevated levels of Staphylococcus aureus and S. epidermidis, along with reduced Cutibacterium, indicative of a dysbiotic profile. Ciclopirox effectively reduces these pathobionts while preserving beneficial taxa, highlighting its potential as a microbiome-friendly antifungal therapy.

Key implications

The review positions CPX/CPO as an underutilized multi-target agent with broad therapeutic value. In dermatology, they outperform many topical antifungals and reduce relapse in seborrheic dermatitis. Their low resistance potential and anti-inflammatory activity make them preferable to corticosteroid combinations. Outside dermatology, they show promise in cancer, HBV, HIV, SARS-CoV-2, polycystic kidney disease, type I diabetes, and stroke. Their iron-chelating mechanism offers a powerful avenue for targeting microbial virulence and host-pathogen interactions, which aligns with emerging interest in microbial metallomics and host–microbiome–metal ion dynamics.