Investigating the Anticancer Activity of Isatin/Dihydropyrazole Hybrids

A series of isatin-dihydropyrazole hybrids have been synthesized in order to assess their potential as anticancer agents. In particular, twelve compounds were evaluated for their anti-proliferative activity toward A549, IGR39, U87, MDA-MB-231, MCF-7, BT474, BxPC-3, SKOV-3, H1299 cell lines, and human foreskin fibroblasts. Four compounds exhibited an interesting anti-proliferative activity and were further exam-ined to determine their EC50 values toward a panel of selected tumor cell lines. 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 chlorine atom or a methyl moiety in the position 5 of the isatin nucleus is beneficial for the antitumor activity. EMAC4001 resulted the most promising compound within the studied series with EC50 values ranging from 0.01 μM to 0.38 μM.