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

Abstract

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 ± 0.54µM respectively, compared to the Doxorubicin IC50 value of 9.11 ± 0.54 and 8.47 ± 0.47µM. Compound 4i also indicated good activity with IC50 value of 9.85 ± 0.69μM on par with Doxorubicin against MCF-7 cells. Compound 4g demonstrated best activity on par with standard reference to IC50 value of 8.52 ± 0.62μM 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.