Synthesis and biological evaluation of novel Mannich bases of 2-arylimidazo[2,1-b]benzothiazoles as potential anti-cancer agents

A new series of Mannich bases of 2-arylimidazo[2,1-b]benzothiazoles were synthesized and evaluated for their anti-cancer activity. These compounds showed better cytotoxicity activity with IC50 values ranging from 2.8 to 8.0 μM in HepG2, MCF-7 and HeLa cell lines. Further mechanism aspects responsible for the anti-cancer activity of two promising compounds 3c and 3f in HepG2 cell line were studied. Interestingly, 3c, 3f induced G2/M cell cycle arrest with down regulation of cyclin B and up regulation of Chk2 protein. Moreover, compounds 3c, 3f also showed the characteristic features of apoptosis such as enhancement in the levels of caspase-3. Treatments with compounds led to a decrease in levels of vital cell proliferation proteins such as Jun (C-Jun, JunB), p38 MAPK, p-JNK and PKCα. The compound 3f of the series could be considered as the potential lead for its development as a novel anti-cancer agent.

Graphical abstractA new class of Mannich bases of 2-arylimidazo[2,1-b]benzothiazoles as potential anti-cancer agents derivatives were prepared and evaluated for their anti-cancer activity including mechanism aspects.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Compounds exhibited profound cytotoxicity in HepG2 cells. ► Compounds caused G2/M cell cycle arrest with inhibitory activity on tubulin. ► Compounds caused decrease in CyclinB1 and increase in caspase-3, Chk2 proteins. ► NF-kB, Jun and MAPK that cause active cell proliferation was down regulated.