Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
Bioorg Med Chem. 2023 Sep 7;92:117439. doi: 10.1016/j.bmc.2023.117439. Epub 2023 Aug 9.
Vincamine is a naturally occurring indole alkaloid showing antioxidant activity and has been used clinically for the prevention and treatment of cerebrovascular disorders and insufficiencies. It has been well documented that antioxidants may contribute to cancer treatment, and thus, vincamine has been investigated recently for its potential antitumor activity. Vincamine was found to show cancer cell cytotoxicity and to modulate several important proteins involved in tumor growth, including acetylcholinesterase (AChE), mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), and T-box 3 (TBX3). Several bisindole alkaloids, including vinblastine and vincristine and their synthetic derivatives, vindesine, vinflunine, and vinorelbine, have been used as clinically effective cancer chemotherapeutic agents. In the present review, the discovery and development of vincamine as a useful therapeutic agent and its antioxidant and antitumor activity are summarized, with its antioxidant-related mechanisms of anticancer potential being described. Also, discussed herein are the design of the potential vincamine-based oncolytic agents, which could contribute to the discovery of further new agents for cancer treatment.
长春胺是一种天然存在的吲哚生物碱，具有抗氧化活性，已在临床上用于预防和治疗脑血管疾病和功能不全。抗氧化剂可能有助于癌症治疗，这一事实已得到充分证实，因此，长春胺最近因其潜在的抗肿瘤活性而受到研究。研究发现长春胺具有癌细胞细胞毒性，并调节肿瘤生长中涉及的几种重要蛋白质，包括乙酰胆碱酯酶 (AChE)、丝裂原激活的蛋白激酶 (MAPK)、核因子-κB (NF-κB)、红细胞生成 2 相关因子 2 (Nrf2) 和 T 盒 3 (TBX3)。几种双吲哚生物碱，包括长春碱和长春新碱及其合成衍生物长春瑞滨、长春氟宁和长春地辛，已被用作临床有效的癌症化疗药物。在本综述中，总结了长春胺作为一种有用的治疗剂的发现和发展及其抗氧化和抗肿瘤活性，并描述了其与抗氧化相关的抗癌潜力机制。此外，本文还讨论了潜在基于长春胺的溶瘤剂的设计，这可能有助于发现更多用于癌症治疗的新药物。
