Crocetin is a promising phyto-based molecule to treat Alzheimer’s disease (AD). The chemical structure of crocetin is incongruent with various standard structural features of CNS drugs. As poor pharmacokinetic behavior is the major hurdle for any candidate to become a drug, we elucidated its druggable characteristics by implementing in silico, in vitro, and in vivo approaches, as limited ADME/PK information is available. Results demonstrate several attributes of crocetin based on rules of drug-likeness, lipophilicity, pK_a, P-gp inhibitory activity, plasma stability, RBC partitioning, metabolic stability, CYP inhibitory action, blood-brain barrier (BBB) permeability, oral bioavailability, and pharmacokinetic interaction with marketed anti-Alzheimer’s drugs (memantine, donepezil, galantamine, and rivastigmine). However, aqueous solubility, chemical stability, plasma protein binding, and P-gp induction are some concerns associated with this molecule that should be taken into consideration during its further development. Overall results indicate favorable ADME/PK behavior and potential druggable candidature of crocetin.

中文翻译：

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藏红花酸的 ADME/PK 见解：一种具有类似药物特征的不寻常化学结构的分子


藏红花酸是一种很有前景的植物分子，可用于治疗阿尔茨海默病 (AD)。藏红花酸的化学结构与中枢神经系统药物的各种标准结构特征不一致。由于较差的药代动力学行为是任何候选药物成为药物的主要障碍，由于可用的 ADME/PK 信息有限，我们通过计算机模拟、体外和体内方法阐明了其可成药特性。结果根据药物相似性、亲脂性、pK _a 、P-gp 抑制活性、血浆稳定性、RBC 分配、代谢稳定性、CYP 抑制作用、血脑屏障 (BBB) 规则证明了藏红花酸的几个属性。 ）渗透性、口服生物利用度以及与市售抗阿尔茨海默病药物（美金刚、多奈哌齐、加兰他敏和卡巴拉汀）的药代动力学相互作用。然而，水溶性、化学稳定性、血浆蛋白结合和 P-gp 诱导是与该分子相关的一些问题，在其进一步开发过程中应予以考虑。总体结果表明藏红花酸具有良好的 ADME/PK 行为和潜在的药物候选资格。