Anticryptococcal Evaluation of the Allylimine 3H2: Modulation of Virulence Traits and Synergistic Action with Amphotericin B
The development of new antifungal scaffolds is critical for expanding therapeutic options against cryptococcosis. Here, we evaluated the allylimine 3H2 as a potential lead compound against Cryptococcus gattii. The allylimine 3H2 exhibited consistent in vitro activity with a geometric mean MIC of 7.5 μg mL–1 across 12 strains and showed a synergistic interaction with amphotericin B, with FICI values reaching 0.5. The compound impaired major virulence determinants, reducing capsule size, melanin synthesis, and laccase activity while altering the negative surface charge. In a murine model, 3H2 potentiated amphotericin B therapy, extending survival to over 100 days and markedly lowering fungal burden in both lungs and brain. Docking simulations supported interactions of 3H2 with targets involved in melanin biosynthesis and cell wall-associated processes. These findings highlight 3H2 as a promising scaffold for antifungal drug discovery and support its further optimization as a candidate for combination therapy against cryptococcosis.
Authors
- Heber Victor Tolomeu (ORCID: https://orcid.org/0000-0002-1022-0598)
- Cleiton Moreira da Silva (ORCID: https://orcid.org/0000-0001-9913-8971)
- Luíza Braga Ferreira dos Santos (ORCID: https://orcid.org/0000-0001-6592-3971)
- Gabriella Freitas Ferreira (ORCID: https://orcid.org/0000-0001-6842-1934)
- Julliana Ribeiro Alves dos Santos (ORCID: https://orcid.org/0000-0001-6918-1186)
- Ângelo de Fátima (ORCID: https://orcid.org/0000-0003-2344-5590)
- Thaís Furtado Ferreira Magalhães
- Marliete Carvalho da Costa
- Vanessa Da Silva Dutra de Carvalho
- Daniel Assis Santos (ORCID: https://orcid.org/0000-0002-1108-5666)
- Maria Aparecida de Resende-Stoianoff
- Cleide Viviane Buzanello
- Danielle Letícia Silva
Institutions
- Universidade Federal de Juiz de Fora (BR)
- Universidade Federal de Minas Gerais (BR)
- Universidad de Salamanca (ES)
- Universidade Estadual do Oeste do Paraná (BR)
- Centro de Estudos e Pesquisa em Saúde Coletiva (BR)
- Instituto de Ciencias Tecnológicas (CL)
- Universidade Ceuma (BR)
- Institute of Organic Chemistry (HU)
- Escola Superior de Ciências da Saúde (BR)
- Instituto de Biología Funcional y Genómica (ES)
- Atatürk University (TR)
- Universidade de Pernambuco (BR)
- Freie Universität Berlin (DE)
Publication Details
- Journal
- ACS Omega
- Published
- 2026-04-26
- DOI
- https://doi.org/10.1021/acsomega.6c01027
- Primary Topic
- Fungal Infections and Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00