{"title":"深入了解咪唑并[1,2-a]吡啶衍生物作为抗癌剂的药用特性。","authors":"Ankush Kumar, Vishakha Sharma, Tapan Behl, Subbulakshmi Ganesan, Deepak Nathiya, Monica Gulati, Mohammad Khalid, Gehan M. Elossaily, Sridevi Chigurupati, Monika Sachdeva","doi":"10.1002/ardp.202400402","DOIUrl":null,"url":null,"abstract":"<p>Cancer ranks among the most life-threatening diseases worldwide and is continuously affecting all age groups. Consequently, many research studies are being carried out to develop new cancer treatments, but many of them experience resistance and cause severe toxicity to the patients. Therefore, there is a continuous need to design novel anticancer agents that are target-based, have a higher potency, and have minimal toxicity. The imidazo[1,2-<i>a</i>]pyridine (IP) pharmacophore has been found to be a prominent moiety in the field of medicinal chemistry due to its vast biological properties. Also, it holds immense potential for combating cancer with minimal side effects, depending on the substitution patterns of the core structure. IPs exhibit significant capability in regulating various cellular pathways, offering possibilities for targeted anticancer effects. The present review summarizes the anticancer profile of numerous IP derivatives synthesized and developed by various researchers from 2016 till now, as inhibitors of phosphoinositide-3-kinase/mammalian target of rapamycin (PI3K/mTOR), protein kinase B/mammalian target of rapamycin (Akt/mTOR), aldehyde dehydrogenase (ALDH), and tubulin polymerization. This review provides a comprehensive analysis of the anticancer activity afforded by the discussed IP compounds, emphasizing the structure–activity-relationships (SARs). 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引用次数: 0
摘要
癌症是全世界威胁生命最严重的疾病之一,并持续影响着各个年龄段的人群。因此,许多研究都在开发新的癌症治疗方法,但许多治疗方法都会产生抗药性,并对患者造成严重的毒副作用。因此,人们不断需要设计出基于靶点、药效更强、毒性最小的新型抗癌药物。咪唑并[1,2-a]吡啶(IP)药理学结构因其广泛的生物特性而成为药物化学领域的一个重要分子。此外,根据核心结构的取代模式,它还具有抗癌的巨大潜力,且副作用极小。IPs 在调节各种细胞通路方面表现出强大的能力,为靶向抗癌提供了可能性。本综述总结了 2016 年至今不同研究人员合成和开发的众多 IP 衍生物的抗癌概况,这些衍生物可作为磷酸肌醇-3-激酶/哺乳动物雷帕霉素靶标(PI3K/mTOR)、蛋白激酶 B/哺乳动物雷帕霉素靶标(Akt/mTOR)、醛脱氢酶(ALDH)和小管蛋白聚合的抑制剂。本综述全面分析了所讨论的 IP 化合物的抗癌活性,并强调了结构-活性-关系(SAR)。其目的还在于强调 IP 分子作为一种有效的部分结构对即将进行的抗癌药物开发的潜在治疗前景,并为合理药物设计领域的研究人员提供帮助。
Insights into medicinal attributes of imidazo[1,2-a]pyridine derivatives as anticancer agents
Cancer ranks among the most life-threatening diseases worldwide and is continuously affecting all age groups. Consequently, many research studies are being carried out to develop new cancer treatments, but many of them experience resistance and cause severe toxicity to the patients. Therefore, there is a continuous need to design novel anticancer agents that are target-based, have a higher potency, and have minimal toxicity. The imidazo[1,2-a]pyridine (IP) pharmacophore has been found to be a prominent moiety in the field of medicinal chemistry due to its vast biological properties. Also, it holds immense potential for combating cancer with minimal side effects, depending on the substitution patterns of the core structure. IPs exhibit significant capability in regulating various cellular pathways, offering possibilities for targeted anticancer effects. The present review summarizes the anticancer profile of numerous IP derivatives synthesized and developed by various researchers from 2016 till now, as inhibitors of phosphoinositide-3-kinase/mammalian target of rapamycin (PI3K/mTOR), protein kinase B/mammalian target of rapamycin (Akt/mTOR), aldehyde dehydrogenase (ALDH), and tubulin polymerization. This review provides a comprehensive analysis of the anticancer activity afforded by the discussed IP compounds, emphasizing the structure–activity-relationships (SARs). The aim is also to underscore the potential therapeutic future of the IP moiety as a potent partial structure for upcoming cancer drug development and to aid researchers in the field of rational drug design.
期刊介绍:
Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.