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

• Published in: ChemistrySelect (Weinheim) 2018-09, Vol.3 (36), p.10250-10254
• Main Authors: Li, Wei, Zhao, Shi‐Jia, Gao, Feng, Lv, Zao‐Sheng, Tu, Jun‐Ying, Xu, Zhi
• Format: Article
• Language: English
• Subjects: anti-HIV; anti-mycobacterial; anti-tumor activity; bis-isatin; diethylene glycol; structure-activity relationship
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.201802185

A series of diethylene glycol tethered bis‐istain derivatives 4 a‐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 49.73 μM. The most active derivative 4 d 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. A series of diethylene glycol tethered bis‐istain derivatives were designed, synthesized and screened for their biological activities in this paper. Eight bis‐isatin derivatives displayed broad‐spectrum activity against all tested drug‐sensitive and drug‐resistant cancer cell lines, and 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 screened for their anti‐mycobacterial and anti‐HIV activities, but the majority of them only exhibited weak to moderate anti‐mycobacterial and anti‐HIV activities.