化学
药理学
麦角甾醇
抗真菌
体内
药品
舍曲林
隐球菌性脑膜炎
抗抑郁药
药物发现
体外
微生物学
生物化学
人类免疫缺陷病毒(HIV)
医学
病毒学
生物
生物技术
内分泌学
病毒性疾病
海马体
作者
Wang Li,Zhaolin Yun,Changjin Ji,Jie Tu,Wanzhen Yang,Jian Li,Na Liu,Chunquan Sheng
标识
DOI:10.1021/acs.jmedchem.1c01845
摘要
Treatment of life-threatening cryptococcal meningitis (CM) is highly challenging due to the limited efficacy of the available antifungal drugs. Antidepressant sertraline (SER) has been 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. It acted by blocking the biosynthesis of ergosterol through the inhibition of Δ5,6-desaturase. This study provides a new target and a drug-like candidate for CM treatment.
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