Synthesis and In Vitro Anti-Tumor, Anti-Mycobacterial and Anti-HIV Activities of Diethylene-Glycol-Tethered Bis-Isatin Derivatives

A series of diethylene glycol tethered bis-istain derivatives 4a-o were designed, synthesized and screened for their biological activities in this paper. Eight bis-isatin derivatives displayed broad-spectrum activities against all tested drug-sensitive and drug-resistant cancer cells with IC50 in a range of 8.32 to 49.73M. The most active derivative 4d was >2.5 folds more potent than etoposide against Hela, HCT-116, A549 and drug-resistant MCF-7/DOX (Doxorubicin-resistant MCF-7) cells and was comparable to etoposide against DU145, SKOV3 and MCF-7. Tubulin inhibitory results suggested that this kind of bis-istain derivatives could exert their anti-cancer activities through tubulin inhibition. The eight bis-isatin derivatives with high anti-tumor activity were selected for further screen to investigate their anti-mycobacterial and anti-HIV activities, but the majority of them only exhibited weak to moderate activities.