Anticryptococcal Evaluation of the Allylimine 3H2: Modulation of Virulence Traits and Synergistic Action with Amphotericin B
Year: 2026
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide 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.
Source: ACS Omega
Authors: Thais Furtado Ferreira Magalhães, Heber Victor Tolomeu, Luíza Braga Ferreira dos Santos, Cleide Viviane Buzanello, Danielle Letícia Silva, Gabriella Freitas Ferreira, Julliana Ribeiro Alves dos Santos, Marliete Carvalho da Costa, Vanessa da Silva Dutra de Carvalho, Daniel Assis Santos, Cleiton Moreira da Silva, Maria Aparecida de Resende-Stoianoff, Ângelo de Fátima
Institutions: Universidade Federal de Minas Gerais, Freie Universität Berlin, Universidade Estadual do Oeste do Paraná, Universidade Federal de Juiz de Fora, Universidade de Pernambuco, Universidade Ceuma, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Instituto de Biología Funcional y Genómica, Atatürk University
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,935
Funders: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Ministério da Ciência, Tecnologia e Inovação, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Financiadora de Estudos e Projetos, Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Universidade Federal de Minas Gerais
Awards: G1384181827, G1426168670, SÍNTESE DE POTENCIAIS INIBIDORES DE UREASE PARA FINS AGRÍCOLAS E MEDICINAIS, G22113365, G2823776494, G3252129808, G3690646728, G3795596884, G3841115575, REDE MINEIRA DE BIOESTIMULANTES E FERTILIZANTES DE EFICIÊNCIA AUMENTADA, G5005883057, INCT EM INIBIDORES DE UREASE DE INTERESSE AGRÍCOLA E MEDICINAL, G5752159476
OpenAlex ID: W7156018047