选择性COX-2抑制剂的开发:从合成到增强疗效通过纳米配方
Marwa Elewa1, Mohamed Shehda2, Pierre A Hanna3
1Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University Ismailia Egypt marwa_elewa@pharm.suez.edu.eg msaid123eg@yahoo.com yasmine_abdelaziz@pharm.suez.edu.eg.
RSC advances
|October 21, 2024
概括
新型烯衍生物被合成为选择性循环氧化酶-2 (COX-2) 抑制剂,用于治疗炎症. 化合物VIIa在体外表现出强烈的活性,但在体内表现不佳,使用尼奥索姆纳米载体提高了其生物可用性.
科学领域:
- 药用化学 医学化学
- 药理学 药理学是指药理学的学科.
- 纳米技术纳米技术
背景情况:
- 非类固醇抗炎药物 (NSAIDs) 通过抑制循环氧化酶 (COX) 酶来控制疼痛和炎症.
- 选择性COX-2抑制是开发具有减少副作用的抗炎药物的关键目标.
- 结构-活性关系 (SAR) 研究指导新型治疗化合物的设计.
研究的目的:
- 设计和合成新型的2 - 胺 - - - - - - - - - - - 胺衍生物作为选择性COX-2抑制剂.
- 评估合成化合物的体外抗炎活性和体内生物可用性.
- 为了提高一个有前途的候选人的体内性能,使用尼奥索姆纳米载体配方.
主要方法:
- 基于已知COX-2抑制剂的SAR的新型 thiophene衍生物的合成.
- 在体外评估COX-2抑制,选择性和抗炎活性 (蛋白质变性试验).
- 分子对接,利宾斯基的五项规则 (RO5) 评估,和尼奥准备 (薄膜水化),然后进行表征 (TEM,DSC) 和药物释放研究.
主要成果:
- 化合物VIA被证明具有选择性的COX-2抑制 (IC50=0.29μM,SI=67.24) 和强大的体外抗炎活性 (IC50=0.54μM).
- 分子对接表明VIIa与COX-2的高结合亲和力.
- 尽管在体外具有有利的特性和符合RO5,但由于水溶性低,VIIa在体内表现出较差的活性.
- 尼奥索姆配方的VIIa导致颗粒大小<200nm,高捕获效率,并显著改善药物释放特征.
结论:
- 新型烯衍生物作为具有显著的体外抗炎作用的选择性COX-2抑制剂具有前景.
- 体封装有效地解决了化合物VIIa的生物可用性限制,增强了其在体内应用的潜力.
- 这项研究突出了体纳米载体在改善难溶性抗炎药物的治疗疗效方面的潜力.
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