Prasher Parteek, Sharma Mousmee, Fatima Rabab, Setzer William N, Sharifi-Rad Javad
Department of Chemistry, University of Petroleum & Energy Studies, Energy Acres, Dehradun, 248007, India.
Department of Chemistry, Uttaranchal University, Dehradun, 248007, India.
Med Oncol. 2025 Sep 20;42(11):485. doi: 10.1007/s12032-025-03005-8.
α-Bisabolol is a naturally derived monocyclic sesquiterpene, abundantly present in German chamomile (Matricaria recutita) and various other aromatic plants and is also increasingly accessible via metabolic engineering platforms. The physicochemical profile and ADMET characteristics of α-bisabolol, suggest a high gastrointestinal absorption, and minimal P-glycoprotein and CYP450 interactions, which validate its drug-like potential. The multi-protein target engagement and predicted activity spectrum of α-bisabolol have been discussed in the manuscript by using in silico tools (SwissTargetPrediction and PASS), which aligns with the experimental anticancer results of α-bisabolol in leukemia, pancreatic, lung, and glioblastoma models. Mechanistically, the anticancer profile of α-bisabolol arises from the induction of mitochondrial apoptosis, disruption of PI3K/Akt/FAK/BRAF pathways, modulation of lipid-raft-associated Bid protein, and dysregulation of autophagy. The design and bioactivity of novel chemical derivatives (e.g., acyl, glycoside, and thiosemicarbazone analogs) and delivery systems (cyclodextrin inclusion complexes, PLGA nanoparticles), emphasizing improvements in solubility, potency, and systemic delivery have also been comprehensively discussed in this review. Finally, a critical evaluation of the clinical translation barriers including poor aqueous solubility, limited in vivo pharmacokinetics, CYP2C9/CYP2J-mediated metabolism, and formulation challenges of α-bisabolol have been succinctly provided. Overall, this review integrates phytochemistry, polypharmacology, mechanistic validation, and translational hurdles, thereby offering a novel roadmap for developing α-bisabolol as a viable anticancer therapeutic.
α-红没药醇是一种天然衍生的单环倍半萜，大量存在于德国洋甘菊（母菊）和其他多种芳香植物中，并且通过代谢工程平台也越来越容易获得。α-红没药醇的物理化学特性和ADMET特征表明其胃肠道吸收性高，与P-糖蛋白和细胞色素P450的相互作用最小，这证实了其类药物潜力。在本手稿中，通过使用计算机工具（SwissTargetPrediction和PASS）讨论了α-红没药醇的多蛋白靶点结合和预测的活性谱，这与α-红没药醇在白血病、胰腺癌、肺癌和胶质母细胞瘤模型中的实验抗癌结果一致。从机制上讲，α-红没药醇的抗癌谱源于线粒体凋亡的诱导、PI3K/Akt/FAK/BRAF通路的破坏、脂筏相关Bid蛋白的调节以及自噬的失调。本综述还全面讨论了新型化学衍生物（如酰基、糖苷和硫代半卡巴腙类似物）和递送系统（环糊精包合物、聚乳酸-羟基乙酸共聚物纳米颗粒）的设计和生物活性，强调了在溶解度、效力和全身递送方面的改进。最后，简要介绍了对α-红没药醇临床转化障碍的批判性评估，包括水溶性差、体内药代动力学有限、CYP2C9/CYP2J介导的代谢以及制剂挑战。总体而言，本综述整合了植物化学、多药理学、机制验证和转化障碍，从而为将α-红没药醇开发成为一种可行的抗癌治疗药物提供了一条新的路线图。
