Background: Dibenzofuran ring is a typical heterocyle that is found in many natural sources and its derivatives exhibit a wide scale of biological applications similar to its analog ring systems; furan and benzofuran.,Materials and Methods: Novel N-(2-methoxydibenzofuran-3-yl)-2-aryloxyacetamide derivatives (2a-I) were synthesized and evaluated for their cytotoxic activity against A549 lung cancer and NIH/3T3 mouse embryofibroblast cell lines. The inhibition percentages of cathepsin D, L, acetylcholinesterase (AChE) and butrylcholinesterase (BuChE) enzymes provoked by the compounds were also determined.,Results and Discussion: Most of the compounds exhibited significant cytotoxicity whose IC 50 values were identified lower than the tested lowest concentration (<3.90 mu g/mL). Compound 2i against cathepsin D and compound 2k against cathepsin L displayed the highest inhibitory activity. Regrettably, the compounds demonstrated very weak AChE and BuChE inhibition.,Conclusion: Compounds 2b, 2c, 2e, 2i and 2k exhibited the highest antiproliferative activity against A549 cell lines with selective profile. However, they did not display satisfying results on tested enzymes.