Ultrasound Assisted Synthesis of 2-Substituted Benzofurans via One-Pot and Sequential Method: Their In Vitro Evaluation

Author(s):

Bodapati V.D. Rao, Suryadevara V. Vardhini, Deepti Kolli, Mandava V.B. Rao* and Manojit Pal*   Pages 580 - 588 ( 9 )

Abstract:

<P>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. </P><P> 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. </P><P> 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. </P><P> 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. </P><P> 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.</P>

Keywords:

Benzofuran, ultrasound, Pd/C, cancer, bioactive compounds, one-pot synthesis.

Affiliation:

Department of Chemistry, Krishna University, Machilipatnam-521 001, Andhra Pradesh, Department of Chemistry, Amritasai Institute of Science and Technology, Paritala, Krishna Dist., 521 180, Andhra Pradesh, Department of Chemistry, Koneru Lakshmaiah Education Foundation, Green fields, Vaddeswaram-522502, Andhra Pradesh, Department of Chemistry, Krishna University, Machilipatnam-521 001, Andhra Pradesh, Dr. Reddy’s Institute of Life Sciences, University of Hyderabad Campus, Hyderabad-500046

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