Discovery of Novel Sertraline Derivatives as Potent Anti-<i>Cryptococcus</i> Agents
作者:Wang Li、Zhaolin Yun、Changjin Ji、Jie Tu、Wanzhen Yang、Jian Li、Na Liu、Chunquan Sheng
DOI:10.1021/acs.jmedchem.1c01845
日期:2022.5.12
proposed to be a potential antifungal agent for CM. However, clinical studies indicated that SER failed to achieve the expected therapeutic effects. Herein, novel SER derivatives were designed by scaffold hopping, and they showed improved anticryptococcal activity both in vitro and in vivo. In particular, compound D16 was identified as a promising anti-CM agent with a new antifungal mode of action.
由于现有抗真菌药物的疗效有限,治疗威胁生命的隐球菌性脑膜炎 (CM) 极具挑战性。抗抑郁药舍曲林 (SER) 已被提议作为 CM 的潜在抗真菌剂。然而,临床研究表明SER未能达到预期的治疗效果。在此,通过支架跳跃设计了新型 SER 衍生物,它们在体外和体内均显示出改善的抗隐球菌活性。特别是,化合物D16被鉴定为具有新的抗真菌作用模式的有前途的抗 CM 剂。它的作用是通过抑制 Δ 5,6来阻断麦角甾醇的生物合成-去饱和酶。该研究为CM治疗提供了一个新的靶点和类药物候选者。