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半胱天冬酶-3:癌症治疗中天然和合成化合物的主要作用靶点。

Caspase-3: A primary target for natural and synthetic compounds for cancer therapy.

作者信息

Yadav Poonam, Yadav Ramakant, Jain Shweta, Vaidya Ankur

机构信息

Department of Pharmacology and Toxicology, NIPER, Hajipur, India.

Department of Neurology, Uttar Pradesh University of Medical Sciences, Saifai, India.

出版信息

Chem Biol Drug Des. 2021 Jul;98(1):144-165. doi: 10.1111/cbdd.13860. Epub 2021 May 20.

Abstract

Caspases, a group of protease enzymes (cysteine proteases), exist as inactive zymogens in the cells and execute apoptosis (programmed cell death). Caspase-3, an executioner caspase, plays an imperative role in apoptosis and becomes a primary target for cancer treatment. A number of analogues of quinazoline, quinazolinone, indoloquinazolines, quinone, naphthoquinones, pyrroloiminoquinones, styrylquinolines, tetheredtetrahydroquinoline, fluoroquinolone, thiosemicarbazones, benzotriazole, pyrimidines, chalcone, and carbazoles have been reported till date, representing caspase-3 mediated apoptosis for cancer therapy. Simultaneously, plant isolates, including lysicamine, podophyllotoxin, and majoranolide, have also been claimed for caspase-3-mediated apoptosis-induced cytotoxicity. Procaspase-activating compound-1 (PAC-1) is the first FDA approved orphan drug, and its synthetic derivative WF-208 also showed fascinating caspase-3 mediated anticancer activity. Till date, a large number of compounds have been reported and patented for their caspase-3-mediated cytotoxicity and now scientist is also focusing to introduce new compounds in market to encompass anticancer activity.

摘要

半胱天冬酶是一组蛋白酶(半胱氨酸蛋白酶),在细胞中以无活性的酶原形式存在,并执行细胞凋亡(程序性细胞死亡)。半胱天冬酶-3是一种执行性半胱天冬酶,在细胞凋亡中起关键作用,成为癌症治疗的主要靶点。迄今为止,已报道了许多喹唑啉、喹唑啉酮、吲哚喹唑啉、醌、萘醌、吡咯并亚氨基醌、苯乙烯基喹啉、 tetheredtetrahydroquinoline、氟喹诺酮、硫代氨基脲、苯并三唑、嘧啶、查耳酮和咔唑的类似物,它们代表了用于癌症治疗的半胱天冬酶-3介导的细胞凋亡。同时,包括石蒜碱、鬼臼毒素和大内酯在内的植物提取物也被认为具有半胱天冬酶-3介导的凋亡诱导细胞毒性。前半胱天冬酶激活化合物-1(PAC-1)是首个获得美国食品药品监督管理局(FDA)批准的孤儿药,其合成衍生物WF-208也显示出迷人的半胱天冬酶-3介导的抗癌活性。迄今为止,已有大量化合物因其半胱天冬酶-3介导的细胞毒性而被报道和申请专利,现在科学家们也在致力于将新化合物推向市场以涵盖抗癌活性。

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