作为选择性hCA IX和XII抑制剂的6-氨基库马林氧化/硫胺:合成,评估和分子动力学研究
Shaik Mahammad Ghouse1, Kareena Sinha1, Alessandro Bonardi2
1Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.
Archiv der Pharmazie
|July 26, 2023
概括
新的库马林衍生物可以选择性地抑制碳酸无水酶IX和XII,这些酶在癌症中过度表达. 这些强大的抑制剂显示出作为新型抗癌剂的前景,提供了有针对性的治疗策略.
科学领域:
- 药用化学 医学化学
- 生物化学 生物化学
- 在瘤学瘤学.
背景情况:
- 在缺氧瘤中,碳酸无水酶IX和XII被上调,促进癌症的进展.
- 这些酶的选择性抑制是开发新型抗癌疗法的关键策略.
研究的目的:
- 合成和评估新型6 - 氨基库马林硫胺和氧化衍生物作为人类碳酸无水酶 (hCA) IX和XII的选择性抑制剂.
- 研究这些衍生物作为抗癌剂的潜力.
主要方法:
- 合成6 - 氨基库马林硫胺和氧基乙烯衍生物.
- 在体外酶抑制对hCA IX和XII的测定.
- 分子对接和动态模拟研究以阐明结合模式.
主要成果:
- 合成的库马林衍生物显示出对hCA IX和XII的选择性和强大的抑制.
- 硫胺衍生物8a显示出亚微分子抑制 (hCA IX的Ki = 0.89 μM,hCA XII的Ki = 0.51 μM).
- 氧化衍生物5n也表现出强烈的抑制 (Ki = 1.055 μM对于hCA IX,Ki = 0.70 μM对于hCA XII).
结论:
- 研究中的库马林衍生物是hCA IX和XII的有效和选择性抑制剂.
- 这些化合物代表了进一步开发抗癌药物的有希望的候选人.
- 分子建模提供了对酶活性部位内的结合相互作用的见解.
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