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*, Manojit Pal*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 20 , Issue 5 , 2020

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Abstract:

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.

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

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VOLUME: 20
ISSUE: 5
Year: 2020
Page: [580 - 588]
Pages: 9
DOI: 10.2174/1871520620666200128120356
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