Biological evaluation of polyhalo 1,3-diazaheterocycle fused isoquinolin-1(2H)-imine derivatives

A series of polyhalo 1,3-diazaheterocycle fused isoquinolin-1(2H)-imines were evaluated in vitro against human tumour cell lines including A431, K562, HL60, HepG2 and Skov-3. As a result, some of the target compounds such as 5b, 5c, 5i, 5o, 6c, 6h and 7f showed stronger cytotoxicity against K562, H562 and Skov-3 cells in comparison with cisplatin, and the others displayed moderate cytotoxicity to A431 and HepG2. Biological investigations using the representative compounds 5c, 6c and 6h were also performed in mice bearing S180 and H22 tumours. The results indicated that these three compounds inhibit S180 and H22 growth. In addition, compounds 6c and 6h have very low acute toxicities. The preliminary analysis of structure–activity relationships is also discussed.

Graphical abstractA series of polyhalo 1,3-diazaheterocycle fused isoquinolin-1(2H)-imines were evaluated for their anti-tumour activities in vitro and in vivo. Some representative compounds showed good anti-tumour activity and low toxicity.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► Polyhalo isoquinolin-1(2H)-imines show excellent cytotoxicity. ► The fluorine atom and intramolecular hydrogen bond can enhance biological activity. ► Polyhalo isoquinolin-1(2H)-imines show good anti-tumour activity in vivo. ► Polyhalo isoquinolin-1(2H)-imines exhibit better levels of safety.