Design, synthesis of benzimidazole tethered 3,4-dihydro-2H-benzo[e] [1, 3] oxazines as anticancer agents

A series of novel 3-(1H-benzo[d]imidazol-2-yl)-3,4-dihydro-2H-benzo[e][1,3] oxazine analogues synthesized through a two-step synthetic protocol. The structure of the compounds were established by interpretation ¹H NMR, ¹³C NMR and Mass spectral data recorded after purification. All the title compounds 4a-k were screened for their in vitro anti-cancer activity against two breast cancer cell lines MCF 7 and MDA-MB-231 by using Doxorubicin as standard reference. Compound 4e displayed superior activity against both the cell lines MCF-7 and MDA-MB-231 with IC₅₀ values of 8.60 ± 0.75 and 6.30 ± 0.54 µM respectively, compared to the Doxorubicin IC₅₀ value of 9.11 ± 0.54 and 8.47 ± 0.47 µM. Compound 4i also indicated good activity with IC₅₀ value of 9.85 ± 0.69 μM on par with Doxorubicin against MCF-7 cells. Compound 4g demonstrated best activity on par with standard reference to IC₅₀ value of 8.52 ± 0.62 μM against MDA-MB-231 cell line. And all other compounds demonstrated good to moderate activity compared to Doxorubicin. Docking studies against EGFR showed that all the compounds have very good binding affinities towards the target. The predicted drug-likeness properties of all compounds enable them to be used as therapeutic agents.