Synthesis and in vitro antitumor activity of new series of benzothiazole and pyrimido[2,1-b]benzothiazole derivatives

•New series of benzothiazoles and pyrimidobenzothiazoles were synthesized.•Nineteen of the synthesized compounds were screened for antitumor activity at NCI, USA.•Compounds 4 (GI50 = 0.77 μM) and 17 (GI50 = 0.44 μM) were proved to be the most active members.

New series of benzothiazole and pyrimido[2,1-b]benzothiazole derivatives were synthesized and characterized by analytical and spectrometrical methods (IR, HRMS, 1H and 13C NMR). Nineteen of the synthesized compounds were selected by the National Cancer Institute (NCI), USA, to be screened for their antitumor activity at a single dose (10 μM) against a panel of 60 cancer cell lines. The most active compounds, 4, 6, 10, 14, 17 and 20 were selected for further evaluation at five dose level screening. Compounds 17 (GI50 = 0.44 μM, TGI = 1.2 μM and LC50 MG-MID = 6.6 μM) and 4 (GI50 = 0.77 μM, TGI = 2.08 μM and LC50 MG-MID = 11.74 μM) were proved to be the most active members in this study. 3D and 2D pharmacophoric maps for the structural features of both compounds were studied.

Graphical abstractCompounds 4 (GI50 = 0.77 μM) and 17 (GI50 = 0.44 μM) were proved to be the most active members in this study.Figure optionsDownload full-size imageDownload as PowerPoint slide