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 3ʹ-deoxy-3ʹ-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, 3ʹ-azide substituted nucleosides (5–8) are more potent compared to ribofuranosyl analogs 1–4. The C-3ʹ-azido analog 8 having anthryl group at 2-position of nucleobase show almost similar potency as that of standard etoposide. [Display omitted] •Synthesis of sugar and base modified benzimidazole nucleosides.•Synthesis was achieved using Vorbrüggen glycosylation reaction.•In-vitro anticancer activity of synthesized nucleoside against MDA-MB-231 cell line was evaluated by MTT assay.•Substituents at benzimidazoles and functionalities at sugar plays an important role for exhibiting anticancer activity.