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糖酶激活的H2S捐赠体,以提高化疗的疗效

Zizhen Ye¹, Jixiang Li¹, Jiarui Shi¹

¹Tianjin Key Laboratory on Technologies Enabling Development of ClinicalTherapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, PR China.

Bioorganic & medicinal chemistry letters

|February 5, 2024

概括

新的癌症疗法使用糖酶激活的硫化 (H₂S) 供体. 这些化合物在对特定酶的反应中释放H2S,有望降低癌细胞活力并提高化疗的有效性.

科学领域:

生物化学生物化学
药用化学医学化学
癌症生物学癌症生物学

背景情况:

硫化 (H2S) 是癌症发育和进展中的关键分子.
针对性地提供治疗剂对于有效的癌症治疗至关重要.

研究的目的:

设计和合成新的糖酶触发硫化 (H2S) 供体.
评估这些H₂S捐赠体在癌症治疗中的疗效,包括它们的组合治疗潜力.

主要方法:

开发H₂S捐赠体,通过通过自燃间隔器将糖分与COS捐赠体结合起来.
在体外和癌细胞中使用特定的探针量化H2S释放.
对HepG2和Hela癌细胞系中细胞毒性和亡诱导的评估.
评估与多克索鲁比辛在联合治疗中的协同效应.

主要成果:

合成的糖化H2S捐赠者在遇到特定的糖化酶时,证明了对H2S的受控释放 (36-67%的效率).
Man1和Man2显著降低了HepG2细胞活力,并诱导了亡.
在HepG2和Hela细胞中,Man1与多克索鲁比结合时表现出协同治疗效应.

结论:

糖酶激活的H₂S捐赠体代表了癌症治疗的有希望的策略.
这些新型化合物提供有针对性的药物输送和增强的治疗结果,特别是在组合疗法.

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