Synthesis of benzimidazole nucleosides and their anticancer activity

An efficient route for the synthesis of benzimidazole nucleosides 1-8 from readily available d-glucose via 3,5-dihydroxy-1,2-O-isopropylidene-α-d-ribofuranose and 3-azido-3-deoxy-1,2-O-isopropylidene-α-d-xylofuranose intermediates has been adopted. Ribofuranosyl nucleosides 1-4 with different benzimidazole bases, and 3'-deoxy-3'-azido-ribofuranosyl nucleosides 5-8, as another series, were obtained. All these newly synthesized analogs were evaluated for anticancer activity using MDA-MB-231 cell line. Among the differently substituted derivatives, 3'-azide substituted nucleosides (5-8) are more potent compared to ribofuranosyl analogs 1-4. The C-3'-azido analog 8 having anthryl group at 2-position of nucleobase show almost similar potency as that of standard etoposide.