硫化释放碳酸无水酶抑制剂有效抑制癌细胞生长
Alessandro Bonardi1, Alessio Nocentini1, Viviana de Luca2
1Department of NEUROFARBA, Pharmaceutical and Nutraceutical Section, University of Firenze, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Florence, Italy.
International journal of molecular sciences
|September 28, 2024
概括
这项研究引入了新的混合分子,将硫化 (H2S) 供体和碳酸酶抑制剂 (CAI) 结合起来用于癌症治疗. 这些化合物通过破坏癌细胞循环和诱导亡,表现出强烈的抗瘤活性.
科学领域:
- 生物化学 生化学
- 在瘤学瘤学.
- 药用化学 医学化学
背景情况:
- 硫化 (H2S) 在高度下表现出抗癌性质.
- 碳酸酶抑制剂 (CAI) 向与瘤相关的异型 (IV,IX,XII),诱导细胞内化和细胞外酸化.
- 向瘤微环境可以恢复对免疫治疗,化疗和放射治疗的敏感性.
研究的目的:
- 开发用于癌症管理的新型治疗剂.
- 研究将H2S供体与CAI结合的协同抗瘤效应.
- 为了评估H2S-CAI混合体对各种癌症细胞系的疗效.
主要方法:
- 合成H2S供体-CA抑制剂 (CAI) 混合体.
- 评估CA抑制和H2S释放动力学.
- 对MDA-MB-231,HCT-116和A549癌细胞系的细胞毒性评估.
- 细胞周期分布和亡诱导的分析.
主要成果:
- 开发的混合化合物有效地抑制了目标碳酸无水酶并释放了H2S.
- 这些化合物在经过测试的癌症细胞系中表现出强烈的剂量依赖性细胞毒性.
- 衍生品30在低氧条件下在HCT-116细胞中表现出增强的细胞毒性 (0.93±0.02μM).
- 混合治疗导致细胞循环停止 (G2 / M,Sub-G1) 和显著的亡诱导.
结论:
- H2S-CAI混合体代表了癌症治疗的有前途的新疗法策略.
- 这些化合物表现出多功能抗瘤作用,包括细胞毒性和亡诱导.
- 开发的杂交品种有可能提高癌症治疗效率.
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