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Updated: Aug 28, 2026

High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method
Published on: May 21, 2018
Synergic Effect of Fluconazole and Quinoline Derivatives Combination Against Cryptococcus spp., Mechanisms of Action
Luana Candice Genz Bazana1,2, Ânderson Ramos Carvalho1,2, Rodrigo Foss da Silva2,3
1Laboratório de Pesquisa em Micologia Aplicada, Universidade Federal do Rio Grande do Sul, Porto Alegre 90620-170, RS, Brazil.
Abstract:
Cryptococcosis is a severe fungal infection affecting immunocompromised individuals, with treatment limited to FLZ, AMB, and FC. This study investigated the antifungal potential of fluconazole (FLZ)-, amphotericin B (AMB)-, 8-hydroxyquinoline (8HQ)-, and clioquinol (CQ)-based combinations against Cryptococcus neoformans and C. gattii. Drug interactions were assessed by checkerboard assay, followed by time-kill curves, irritability, toxicity, and virulence factors inhibition tests. The FLZ + AMB combination showed weak synergism, whereas FLZ combined with CQ or 8HQ exhibited strong synergistic effects (p < 0.001) at low concentrations (0.125-0.25 µg/mL), up to three times greater than those of FLZ + AMB. This effect persisted across other strains, including less FLZ-susceptible isolates. Moreover, FLZ + CQ inhibited melanin production in both species without causing significant irritability or toxicity in the tested models. These results indicate that combining drugs with distinct mechanisms of action can enhance antifungal efficacy while potentially reducing treatment doses. The FLZ + CQ/8HQ combinations represent promising candidates for future in vivo models for therapeutic evaluation.
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