含有甲甲酸盐,维生素D和衍生物的混合分子:合成,表征,体内细胞毒性,在中ADME对接,分子对接和动力学
Zintle Mbese1, Mpho Choene2, Eric Morifi3
1Department of Chemistry, University of Fort Hare, Alice Campus, 5700, Alice, Eastern Cape, South Africa.
Chemistry & biodiversity
|September 15, 2024
概括
结合双酸盐,维生素D,酸或甲状腺酸盐的新混合药物显示出增强癌症治疗的前景. 这些新型化合物表现出强大的抗癌活性和有利的结合亲缘关系,表明改善治疗疗效和减少副作用的潜力.
科学领域:
- 药用化学 医学化学
- 药物发现 药物发现 药物发现
- 在瘤学瘤学.
背景情况:
- 组合疗法是开发有效抗癌药物的关键策略,旨在提高疗效,克服耐药性,减少治疗时间.
- 双酸盐和维生素D用于治疗骨疾病,而基药物和甲醇酸盐是常见的化疗药物,但往往有不良影响.
- 混合基化合物为结合治疗作用和潜在减轻副作用提供了一个有希望的方法.
研究的目的:
- 设计和合成新型混合化合物,包括双酸盐,维生素D,以为基础的或甲甲酸盐的部分.
- 评估合成的混合化合物作为抗癌剂的潜力.
- 研究这些新型杂交体的骨结合亲和力,体外细胞毒性和分子作用机制.
主要方法:
- 使用FTIR,NMR (H,P,C) 和UHPLC-HRMS合成和描述混合化合物.
- 氧酸盐骨结合测定,以评估骨亲和力.
- 在MCF-7和HT-29癌细胞系的体外细胞毒性测定.
- 分子对接,动力学模拟,瑞士ADME,ProTox-II和GUSAR分析.
主要成果:
- 证实了混合化合物的成功合成和表征.
- 双酸盐混合化合物表现出有希望的与酸的结合亲和力.
- 混合体19对HT-29细胞具有显著的细胞毒性,混合体15对MCF-7细胞具有显著的细胞毒性.
- 混合体15表现出强大的结合亲和力 (-9.70 kcal/mol) 的人类3α-基类固醇脱酶3型,表明潜在的抑制活性.
结论:
- 合成的混合化合物代表了抗癌药物开发的有希望的候选人.
- 特定的杂交物显示出向骨转移的潜力,并对癌细胞表现出细胞毒性作用.
- 计算分析表明,某些杂交品具有有利的药理动力学特性和明确的作用机制.
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