Investigating the Anticancer Activity of Isatin/Dihydropyrazole Hybrids

Meleddu, Rita;Petrikaite, Vilma;Distinto, Simona

;Arridu, Antonella;Angius, Rossella;SERUSI, LORENZO;Škarnulytė, Laura;Endriulaitytė, Ugnė;Paškevičiu̅tė, Miglė;Cottiglia, Filippo;Gaspari, Marco;Taverna, Domenico;Deplano, Serenella;Fois, Benedetta;Maccioni, Elias

2019-01-01

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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 50 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. EMAC4001 proved the most promising compound within the studied series with EC 50 values ranging from 0.01 to 0.38 μM.