Synthesis and antifungal activities of phenylhydrazono derivatives as the novel fructose-1,6-bisphosphate aldolase inhibitors
GUO Li1， GUO Yanrong2， REN Yanliang3， HAN Xinya2
1.Hubei Ecological and Environmental Monitoring Center Station， Wuhan 430072， China；2.School of Chemistry and Chemical Engineering， Anhui University of Technology， Maanshan， Anhui 243002， China；3.Laboratory of Pesticide & Chemical Biology， Key Laboratary of Ministry of Education， College of Chemistry， Central China Normal University， Wuhan 430079， China
Abstract：Fructose-1， 6-bisphosphate aldolase from C. albicans (CaFBA-II) is an attractive new target for the discovery of drugs to combat invasive fungal infection. Our previous study demonstrated that β-arylhydrazono-α， γ-dicarbonylderivatives exhibit moderate inhibitory against CaFBA-II. Herein， several new phenylhydrazono derivatives were found to potently inhibit CaFBA-II. The experimental results show that the NO2 group in the R2 position is favorable， but COOH， SO3H and halogen atom are unfavorable for their CaFBA-II inhibitory activities. Especially， when the R3 was substituted by sulfonic acid group， compound 2g possessed the highest inhibitory activity (IC50＝200 nmol·L－1). Furthermore， compound 2g were selected as representative molecule， the binding mode of 2g and the surrounding residues in the active site of CaFBA-II were elucidated by jointly using DOX methods and molecular dynamics (MD) simulations. Notably， antifungal experiments demonstrate that most of our designed compounds possess moderate inhibitory activities (MIC80＝16-64 μg · mL－1) against C. albicans. The present results suggest that the phenylhydrazono derivatives can be used as the lead compounds of novel drugs against fungal pathogens of humans in the future.