基于thioxo的 Kojic 酸衍生物作为具有抗结核和抗皮肤菌潜力的强效铁酶抑制剂
Gülşah Karakaya1, Suat Sari2, Fatma Sezer Senol Deniz3
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, İzmir Katip Çelebi University, İzmir, Türkiye.
Drug development research
|January 27, 2026
概括
新型含硫化合物显示出增强的铁酶抑制和强大的抗菌活性. 用硫基替换碳基显著提高了生物活性,这表明了针对真菌和细菌的新治疗剂的潜力.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 药理学 药理学是指药理学的学科.
背景情况:
- 铁酶抑制剂对于治疗多颜色化疾病至关重要.
- 需要使用抗菌素和抗皮肤菌剂来对抗耐药菌株.
- 开发多功能治疗剂为药物发现提供了一个有前途的战略.
研究的目的:
- 为了合成新的含硫类型的pyran脚手架的类似物.
- 评估这些类似物作为铁酶抑制剂,抗结核和抗皮肤菌剂的生物潜力.
- 调查结构-活性关系,特别是硫基替代的效果.
主要方法:
- 使用已确定的有机化学技术合成含硫类型.
- 通过光谱方法 (NMR,MS) 和元素分析阐明结构.
- 生物评估包括铁酶抑制试验,抗菌菌 (Mycobacterium avium) 和抗皮质菌 (如Trichophyton mentagrophytes) 活性测试,以及细胞毒性试验 (HeLa,MRC-5细胞).
- 分子建模以预测铁酶活性部位内的相互作用.
主要成果:
- 成功合成和结构确认新型含硫的pyran衍生物.
- 在碳基转化为硫基时,显著增强了铁酶抑制,其中6c和6d化合物的IC50值分别为0.143和0.121 mg/mL.
- 蒂奥克索类似物表现出与乙醇相比较的强烈抗菌活性,特别是在对抗Mycobacterium avium.
- 显著的抗皮质素活性,MIC值为1-2μg/mL,对关键皮质素物种有明显的抗皮质素活性.
- 在细胞毒性试验中,化合物在无毒度 (≥128μg/mL) 时显示出生物活性.
结论:
- 用thiocarbonyl功能替换碳基显著提高了pyran衍生物的生物活性.
- 合成的化合物显示出作为多功能治疗剂的显著潜力,特别是作为铁酶抑制剂和抗菌剂.
- 这些发现凸显了这些含硫支架在开发抗超色素和微生物感染的新药方面的领先潜力.
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