Synthesis and anticancer activities of novel 1,2,4-triazolo[3,4-a]phthalazine derivatives

•Two series of novel 1,2,4-triazolo[3,4-a]phthalazine derivatives were synthesized.•Most of these compounds exhibited broad-spectrum cytotoxic activity.•Ph at C-3 was most active in all series.•One of them (Ph at C-3) was more potent than 5-Fu against the four cancer cell lines.•One of them (Ph at C-3) showed cell cycle arrest at G2/M phase and induced apoptosis.

Trying to develop potent and selective anticancer agents, two series of novel 1,2,4-triazolo[3,4-a]phthalazine derivatives were designed and synthesized. Their antitumor activities were evaluated by MTT method against four selected human cancer cell lines (MGC-803, EC-9706, HeLa and MCF-7). Our results showed that compound 11h exhibited good anticancer activities compared to 5-fluorouracil against the four tested cell lines, with IC50 values ranging from 2.0 to 4.5 μM. Flow cytometry analysis indicated that compound 11h induced the cellular early apoptosis and cell cycle arrest at G2/M phase in EC-9706.

Graphical abstractThe compound 11h exhibited IC50 values against the four tested human cancer cell lines ranging from 2.0 to 4.5 μM.Figure optionsDownload full-size imageDownload as PowerPoint slide