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将青蒿素及其衍生物重新用作抗癌药物:机遇还是挑战?

Repurposing Artemisinin and its Derivatives as Anticancer Drugs: A Chance or Challenge?

作者信息

Ma Zhaowu, Woon Clariis Yi-Ning, Liu Chen-Guang, Cheng Jun-Ting, You Mingliang, Sethi Gautam, Wong Andrea Li-Ann, Ho Paul Chi-Lui, Zhang Daping, Ong Peishi, Wang Lingzhi, Goh Boon-Cher

机构信息

School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, China.

Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore.

出版信息

Front Pharmacol. 2021 Dec 31;12:828856. doi: 10.3389/fphar.2021.828856. eCollection 2021.

Abstract

Cancer has become a global health problem, accounting for one out of six deaths. Despite the recent advances in cancer therapy, there is still an ever-growing need for readily accessible new therapies. The process of drug discovery and development is arduous and takes many years, and while it is ongoing, the time for the current lead compounds to reach clinical trial phase is very long. Drug repurposing has recently gained significant attention as it expedites the process of discovering new entities for anticancer therapy. One such potential candidate is the antimalarial drug, artemisinin that has shown anticancer activities and . In this review, major molecular and cellular mechanisms underlying the anticancer effect of artemisinin and its derivatives are summarised. Furthermore, major mechanisms of action and some key signaling pathways of this group of compounds have been reviewed to explore potential targets that contribute to the proliferation and metastasis of tumor cells. Despite its established profile in malaria treatment, pharmacokinetic properties, anticancer potency, and current formulations that hinder the clinical translation of artemisinin as an anticancer agent, have been discussed. Finally, potential solutions or new strategies are identified to overcome the bottlenecks in repurposing artemisinin-type compounds as anticancer drugs.

摘要

癌症已成为一个全球性的健康问题,占全球死亡人数的六分之一。尽管近年来癌症治疗取得了进展,但对易于获得的新疗法的需求仍在不断增长。药物发现和开发过程艰巨且耗时多年,而且在这个过程中,当前的先导化合物进入临床试验阶段的时间非常长。药物重新利用最近受到了广泛关注,因为它加快了发现抗癌治疗新实体的过程。一种这样的潜在候选药物是抗疟药青蒿素,它已显示出抗癌活性。在这篇综述中,总结了青蒿素及其衍生物抗癌作用的主要分子和细胞机制。此外,还综述了这类化合物的主要作用机制和一些关键信号通路,以探索有助于肿瘤细胞增殖和转移的潜在靶点。尽管青蒿素在疟疾治疗方面已有既定的形象,但本文讨论了其药代动力学特性、抗癌效力以及目前阻碍青蒿素作为抗癌药物进行临床转化的制剂。最后,确定了潜在的解决方案或新策略,以克服将青蒿素类化合物重新用作抗癌药物的瓶颈。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a0/8758560/acada6996b63/fphar-12-828856-g001.jpg

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