Investigating the Anticancer Activity of Isatin/Dihydropyrazole Hybrids

ACS Med Chem Lett. 2018 Dec 18;10(4):571-576. doi: 10.1021/acsmedchemlett.8b00596.

Rita Meleddu ¹, Vilma Petrikaite ² ³, Simona Distinto ¹, Antonella Arridu ¹, Rossella Angius ⁴, Lorenzo Serusi ¹, Laura Škarnulytė ², Ugnė Endriulaitytė ², Miglė Paškevičiu Tė ², Filippo Cottiglia ¹, Marco Gaspari ⁵, Domenico Taverna ⁵, Serenella Deplano ¹, Benedetta Fois ¹, Elias Maccioni ¹

Affiliations

1 Department of Life and Environmental Sciences, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.
2 Department of Drug Chemistry, Faculty of Pharmacy, Lithuanian University of Health Sciences, 50162 Kaunas, Lithuania.
3 Institute of Biotechnology, Vilnius University, LT-10257 Vilnius, Lithuania.
4 Laboratorio NMR e Tecnologie Bioanalitiche, Sardegna Ricerche, Pula, 09010 Cagliari, Italy.
5 Department of Experimental and Clinical Medicine, "Magna Græcia" University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy.

PMID: 30996798 DOI: 10.1021/acsmedchemlett.8b00596

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 EC₅₀ 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 EC₅₀ values ranging from 0.01 to 0.38 μM.

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