研究异吲哚酮/二氢吡唑杂化物的抗癌活性。
Investigating the Anticancer Activity of Isatin/Dihydropyrazole Hybrids.
作者信息
Meleddu Rita, Petrikaite Vilma, Distinto Simona, Arridu Antonella, Angius Rossella, Serusi Lorenzo, Škarnulytė Laura, Endriulaitytė Ugnė, Paškevičiu Tė Miglė, Cottiglia Filippo, Gaspari Marco, Taverna Domenico, Deplano Serenella, Fois Benedetta, Maccioni Elias
机构信息
Department of Life and Environmental Sciences, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.
Department of Drug Chemistry, Faculty of Pharmacy, Lithuanian University of Health Sciences, 50162 Kaunas, Lithuania.
出版信息
ACS Med Chem Lett. 2018 Dec 18;10(4):571-576. doi: 10.1021/acsmedchemlett.8b00596. eCollection 2019 Apr 11.
Abstract
A series of isatin-dihydropyrazole hybrids have been synthesized in order to assess their potential as anticancer agents. In particular, 12 compounds were evaluated for their antiproliferative activity toward A549, IGR39, U87, MDA-MB-231, MCF-7, BT474, BxPC-3, SKOV-3, and H1299 cell lines, and human foreskin fibroblasts. Four compounds exhibited interesting antiproliferative activity and were further examined to determine their EC values toward a panel of selected tumor cell lines. The best compounds were then investigated for their induced mechanism of cell death. Preliminary structure-activity relationship indicates that the presence of a substituent such as a chlorine atom or a methyl moiety in position 5 of the isatin nucleus is beneficial for the antitumor activity. proved the most promising compound within the studied series with EC values ranging from 0.01 to 0.38 μM.
摘要
为了评估一系列异吲哚酮-二氢吡唑杂化物作为抗癌剂的潜力，已合成了这些化合物。特别地，评估了12种化合物对A549、IGR39、U87、MDA-MB-231、MCF-7、BT474、BxPC-3、SKOV-3和H1299细胞系以及人包皮成纤维细胞的抗增殖活性。四种化合物表现出有趣的抗增殖活性，并进一步检测以确定它们对一组选定肿瘤细胞系的EC值。然后研究了最佳化合物的细胞死亡诱导机制。初步构效关系表明，异吲哚酮核5位存在氯原子或甲基等取代基有利于抗肿瘤活性。在所研究的系列中被证明是最有前途的化合物，其EC值范围为0.01至0.38μM。
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