Background: In chemistry, the derivatives of benzofuran which are substituted on five-membered ring constitute one of the salient moieties in medicinal field and a survey of literature revealed that a good number of reports have shown that tetrahydrobenzofuran derivatives are of valuable biological activities.

Aim: On the basis of previous survey, we aimed to generate a series of 2-(4-azidobenzoyl)-3-substitutedaryl-6,6-dimethyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one bearing azide group which were identified by anti-cancer screening against sixteen cell-lines of NCI (National Cancer Institute) using nine different cancer cell panels.

Materials and methods: The tetrahydrobenzofuran derivatives were synthesized by multi-component reactions. It was achieved by coupling of dimedone (3.57 mmole), 4-azido phenacyl bromide (3.92 mmole) and various aromatic aldehydes (3.57 mmole) using two different bases i.e. pyridine and N,N- diethylethanamine under reflux condition. Anti-cancer activity was carried out by NCI-60 cell-lines using standard protocol by National Institute of Health.

Results: The results from anti-cancer study shows that the compound 4a exhibited diverse cytotoxic activity against renal cancer panel (UO-31) with significant selectivity and had inhibitory effect on the generation of UO-31 (growth percent= 69.36%) and the compound 4e showed comparable activity in the same cell-line (UO-31: growth percent= 80.86%).

Conclusions: In summary, a series of azide group containing tetrahydrobenzofuran derivatives have been synthesized and were evaluated for their anticancer activity. It was concluded that the derivatives 4a and 4e exhibited promising anticancer activity. Nature of substituent on phenyl ring seems to be the crucial factor affecting the activity in both the compounds.