新药的开发过程因其物理化学不足而受到极大的阻碍,药代动力学,和内在特征。在这方面,选择的氯吲哚酮,(Z)-6-氯-3-(2-氯亚苄基)吲哚啉-2-酮(C1),和硝基吲哚酮,(Z)-6-氯-3-(2-硝基亚苄基)吲哚啉-2-酮(C2),进行了SwissADME和密度泛函理论(DFT)分析。对于化合物C1和C2,BOILED-Egg药代动力学模型预测肠吸收,血脑屏障(BBB)渗透,和P-糖蛋白相互作用。根据理化分析,C1具有适于口服吸收的特殊的药物样特征。尽管只是一些主要CYP450亚型的底物,预计化合物C1和C2具有强的血浆蛋白结合和有效的分布,并阻断这些亚型。使用B3LYP/6-311G的DFT研究(d,P)采用隐含水效应的方法来评估结构特征,电子性质,以及C1和C2的全局反应性参数(GRP)。DFT结果为其他研究提供了进一步的支持,这意味着C2比C1更具水溶性,并且两种化合物都可以与其他分子形成氢键和(弱)分散相互作用,如溶剂和生物分子。此外,GRP研究表明,C1应该比C2更稳定,反应性更低。C1和C2均显示了浓度依赖性的2,2-二苯基-1-吡啶酰肼基(DPPH)和2,2'-氮杂-双(3-乙基苯并噻唑啉-6-磺酸(ABTS)自由基清除活性。简而言之,这一发现为进一步探索这些分子对多种人类疾病的治疗潜力提供了坚实的基础.
The process of developing of new drugs is greatly hampered by their inadequate physicochemical, pharmacokinetic, and intrinsic characteristics. In this regard, the selected chloro indolinone, (Z)-6-chloro-3-(2-chlorobenzylidene)indolin-2-one (C1), and nitro indolinone, (Z)-6-chloro-3-(2-nitrobenzylidene)indolin-2-one (C2), were subjected to SwissADME and density function theory (DFT) analysis. For compounds C1 and C2, the BOILED-Egg pharmacokinetic model predicted intestinal absorption, blood-brain barrier (BBB) penetration, and p-glycoprotein interaction. According to the physicochemical analysis, C1 has exceptional drug-like characteristics suitable for oral absorption. Despite only being substrates for some of the major CYP 450 isoforms, compounds C1 and C2 were anticipated to have strong plasma protein binding and efficient distribution and block these isoforms. The DFT study using the B3LYP/6-311G(d,p) approach with implicit water effects was performed to assess the structural features, electronic properties, and global reactivity parameters (GRP) of C1 and C2. The DFT results provided further support for other studies, implying that C2 is more water-soluble than C1 and that both compounds can form hydrogen bonds and (weak) dispersion interactions with other molecules, such as solvents and biomolecules. Furthermore, the GRP study suggested that C1 should be more stable and less reactive than C2. A concentration-dependent 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2\'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity was shown by both C1 and C2. In brief, this finding has provided a strong foundation to explore further the therapeutic potential of these molecules against a variety of human disorders.