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西红花酸的药代动力学/药物代谢动力学见解：一种具有类药物特性的特殊化学结构分子。

ADME/PK Insights of Crocetin: A Molecule Having an Unusual Chemical Structure with Druglike Features.

作者信息

Manhas Diksha, Dhiman Sumit, Kour Harpreet, Kour Dilpreet, Sharma Kuhu, Wazir Priya, Vij Bhavna, Kumar Ajay, Sawant Sanghapal D, Ahmed Zabeer, Nandi Utpal

机构信息

Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

出版信息

ACS Omega. 2024 May 2;9(19):21494-21509. doi: 10.1021/acsomega.4c02116. eCollection 2024 May 14.

DOI:10.1021/acsomega.4c02116
PMID:38764638
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11097163/
Abstract

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, p, 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.

摘要

藏红花酸是一种有前景的用于治疗阿尔茨海默病（AD）的植物源分子。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。由于不良的药代动力学行为是任何候选药物成为药物的主要障碍，鉴于有限的药物代谢动力学/药物处置（ADME/PK）信息，我们通过实施计算机模拟、体外和体内方法阐明了其成药特性。结果基于类药性、亲脂性、p、P-糖蛋白抑制活性、血浆稳定性、红细胞分配、代谢稳定性、细胞色素P450（CYP）抑制作用、血脑屏障（BBB）通透性、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展示了藏红花酸的几个特性。然而，水溶性、化学稳定性、血浆蛋白结合和P-糖蛋白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行为和潜在的成药候选资格。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11bc/11097163/ed697d47df42/ao4c02116_0009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11bc/11097163/ca2b07596b09/ao4c02116_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11bc/11097163/25b87f697b85/ao4c02116_0006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11bc/11097163/364b7eb83f1a/ao4c02116_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11bc/11097163/ed697d47df42/ao4c02116_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11bc/11097163/209efa234c55/ao4c02116_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11bc/11097163/a2615612e7ec/ao4c02116_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11bc/11097163/8a9f7fa06e43/ao4c02116_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11bc/11097163/e9e6b115a1f9/ao4c02116_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11bc/11097163/ca2b07596b09/ao4c02116_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11bc/11097163/25b87f697b85/ao4c02116_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11bc/11097163/33d0ba2669df/ao4c02116_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11bc/11097163/364b7eb83f1a/ao4c02116_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11bc/11097163/ed697d47df42/ao4c02116_0009.jpg

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