Camacho Jairo, Bejarano Carlos A, Diaz John E, Vargas-Casanova Yerly, Carvajal Silvia Katherine, Diaz Santoyo Valentina, Parra-Giraldo Claudia M, Loaiza Alix E
Departamento de Química, Facultad de Ciencias, Pontificia Universidad Javeriana, Cra. 7 No. 40-62, Bogotá 110231, Colombia.
Departamento de Química, Facultad de Ciencias, Universidad Antonio Nariño, Cra. 3 Este No. 47 A-15, Bogotá 110231, Colombia.
Molecules. 2025 Mar 5;30(5):1165. doi: 10.3390/molecules30051165.
This study reports the synthesis, characterization, and antifungal evaluation of a series of pyridoxal and salicylaldehyde derivatives, using synthetic methodologies such as radical cyclizations and click chemistry. Compounds and , featuring a fused dihydrobenzoxepine-pyridine scaffold, demonstrated effective fungicidal activity with MIC values of 19 µg/mL against 2807. Similarly, compound exhibited notable activity with a MIC of 75 µg/mL against PUJ-HUSI 537. Both compounds outperformed fluconazole (FLC) in these strains. In silico ADMET profiling revealed favorable pharmacokinetic properties, including blood-brain barrier penetration and drug-likeness parameters consistent with Lipinski's rule of five. Cytotoxicity assays on human fibroblasts confirmed the low toxicity of compound at the tested concentrations. These results highlight the potential of the fused dihydrobenzoxepine-pyridine scaffold as a promising antifungal candidate for further investigations.
本研究报告了一系列吡哆醛和水杨醛衍生物的合成、表征及抗真菌评估，采用了自由基环化和点击化学等合成方法。具有稠合二氢苯并氧杂䓬 - 吡啶支架的化合物 和 对 2807 表现出有效的杀真菌活性，MIC 值为 19 µg/mL。同样，化合物 对 PUJ - HUSI 537 的 MIC 为 75 µg/mL，表现出显著活性。在这些菌株中，这两种化合物均优于氟康唑（FLC）。计算机辅助的 ADMET 分析显示出良好的药代动力学性质，包括血脑屏障穿透性以及与 Lipinski 五规则一致的类药性质参数。对人成纤维细胞的细胞毒性试验证实了化合物 在测试浓度下的低毒性。这些结果突出了稠合二氢苯并氧杂䓬 - 吡啶支架作为一种有前景的抗真菌候选物用于进一步研究的潜力。
