Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 121 (Suppl. 1) 2026
Review
Novel targets and potential therapeutic approaches for chromoblastomycosis: phosphatase/peptidase inhibitors and metal-based compounds containing 1,10-phenanthroline
1Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Taxonomia, Bioquímica e Bioprospecção de Fungos, Rio de Janeiro, RJ, Brasil
2Universidade Federal do Rio de Janeiro, Instituto de Microbiologia Paulo de Góes, Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes, Rio de Janeiro, RJ, Brasil
3Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, Rede Micologia RJ, Rio de Janeiro, RJ, Brasil
DOI: 10.1590/0074-02760250305
ABSTRACT
Chromoblastomycosis (CBM) is a chronic, debilitating subcutaneous mycosis that remains a major therapeutic challenge due to its limited responsiveness to conventional antifungal agents. Our research group investigated key cellular mechanisms underlying fungal virulence, persistence, and resistance, revealing that CBM-associated fungi can exhibit ectophosphatase and calcineurin activities, secrete aspartic and metallo-type peptidases, and form highly structured biofilms that reinforce their chronic behaviour and tolerance to treatment. Targeted inhibition of these enzymatic systems using classical inhibitors of peptidases [e.g., human immunodeficiency virus (HIV) aspartic peptidase inhibitors], acid phosphatases (e.g., sodium orthovanadate), and calcineurin (e.g., tacrolimus and cyclosporine A) markedly impaired fungal growth, morphogenesis, biofilm development, and/or host-cell interactions, underscoring their potential roles in key fungal biological processes and infection establishment. Furthermore, coordination compounds incorporating transition metals (e.g., silver) and 1,10-phenanthroline-derived ligands demonstrated potent antifungal efficacy against CBM-associated fungi and may interfere with key physiological and virulence-associated pathways. Collectively, these findings advance the understanding of CBM fungal pathophysiology, unveiling novel molecular targets and highlighting opportunities for alternative therapeutic strategies and antifungal drug development.
key words:
Coordination compounds
HIV peptidase inhibitors
calcineurin inhibitors
antifungal activity
cellular interaction
biofilm
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Financial support: CNPq, FAPERJ, CAPES (financial code 001), FIOCRUZ.
+ Corresponding author: lucimar@ioc.fiocruz.br | 
https://orcid.org/0000-0002-3507-4689
Received 24 October 2025
Accepted 30 January 2026
HOW TO CITE
Sousa IS, Granato MQ, Palmeira VF, Santos ALS, Kneipp LF. Novel targets and potential therapeutic approaches for chromoblastomycosis: phosphatase/peptidase inhibitors and metal-based compounds containing 1,10-phenanthroline. Mem Inst Oswaldo Cruz. 2026; 121(Suppl. 1): e250305.
HANDLING EDITOR
Ana Carolina Paulo Vicente | https://orcid.org/0000-0001-7086-2042
