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Recent Development in Indole Derivatives as Anticancer Agents for Breast Cancer

吲哚试验 PI3K/AKT/mTOR通路 乳腺癌 芳香化酶 癌症 药理学 癌症研究 医学 癌细胞 化学 细胞凋亡 内科学 生物化学
作者
Kamalpreet Kaur,Vikas Jaitak
出处
期刊:Anti-cancer Agents in Medicinal Chemistry [Bentham Science Publishers]
卷期号:19 (8): 962-983 被引量:61
标识
DOI:10.2174/1871520619666190312125602
摘要

Background: Breast Cancer (BC) is the second most common cause of cancer related deaths in women. Due to severe side effects and multidrug resistance, current therapies like hormonal therapy, surgery, radiotherapy and chemotherapy become ineffective. Also, the existing drugs for BC treatment are associated with several drawbacks such as poor oral bioavailability, non-selectivity and poor pharmacodynamics properties. Therefore, there is an urgent need for the development of more effective and safer anti BC agents. Objective: This article explored in detail the possibilities of indole-based heterocyclic compounds as anticancer agents with breast cancer as their major target. Methods: Recent literature related to indole derivatives endowed with encouraging anti BC potential is reviewed. With special focus on BC, this review offers a detailed account of multiple mechanisms of action of various indole derivatives: aromatase inhibitor, tubulin inhibitor, microtubule inhibitor, targeting estrogen receptor, DNA-binding mechanism, induction of apoptosis, inhibition of PI3K/AkT/NFkB/mTOR, and HDAC inhibitors, by which these derivatives have shown promising anticancer potential. Results: Exhaustive literature survey indicated that indole derivatives are associated with properties of inducing apoptosis and disturbing tubulin assembly. Indoles are also associated with the inhibition of NFkB/mTOR/PI3K/AkT and regulation of estrogen-mediated activity. Furthermore, indole derivatives have been found to modulate critical targets such as topoisomerase and HDAC. These derivatives have shown significant activity against breast cancer cells. Conclusion: In BC, indole derivatives seem to be quite competent and act through various mechanisms that are well established in case of BC. This review has shown that indole derivatives can further be explored for the betterment of BC chemotherapy. A lot of potential is still hidden which demands to be discovered for upgrading BC chemotherapy.
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