Background: The 2-substituted benzofuran framework has attracted enormous attention due to its
presence in a range of bioactive compounds and natural products. While various methods for the synthesis of 2-
substituted benzofuran derivatives are known, several of them suffer from certain drawbacks.
Objective: The main objective of this work was to explore a series of 2-(het)aryl substituted benzofurans derivatives
for their cytotoxic properties against cancer cell lines in vitro.
Methods: In our efforts, we have developed a one-pot synthesis of this class of compounds via sequential C-C
coupling followed by C-Si bond cleavage and subsequent tandem C-C/C-O bond-forming reaction under ultrasound
irradiation. The methodology involved coupling of (trimethylsilyl)acetylene with iodoarenes in the presence
of 10% Pd/C-CuI-PPh3-Et3N in MeOH followed by treating the reaction mixture with K2CO3 in aqueous
MeOH and finally coupling with 2-iodophenol. A variety of 2-substituted benzofurans were synthesized using
this methodology in good yield. All the synthesized compounds were tested in vitro against two cancer cell
lines, e.g. MDAMB-231 and MCF-7 cell lines subsequently against SIRT1.
Results: The benzofuran derivative 3m showed encouraging growth inhibition of both MDAMB-231 and MCF-
7 cell lines and significant inhibition of SIRT1. The compound 3m also showed a concentration-dependent
increase in the acetylation of p53.
Conclusion: Our efforts not only accomplished a one-pot and direct access to 2-(het)aryl substituted benzofurans
but also revealed that the benzofuran framework presented here could be a potential template for the
identification of potent inhibitors of SIRT1.