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.
Graphical Abstract
[http://dx.doi.org/10.1016/j.ejmech.2011.04.053] [PMID: 21570749]
[http://dx.doi.org/10.1016/j.jep.2009.05.004] [PMID: 19450674]
[http://dx.doi.org/10.1016/j.bbrc.2008.04.188] [PMID: 18482581]
[http://dx.doi.org/10.1021/jf801289m] [PMID: 18778071]
[http://dx.doi.org/10.1007/s11418-007-0205-0] [PMID: 18404322]
[http://dx.doi.org/10.1016/j.bmc.2005.01.028] [PMID: 15755662]
[http://dx.doi.org/10.1021/np000071b] [PMID: 11141112]
[http://dx.doi.org/10.1021/jm0708634] [PMID: 17948982]
[http://dx.doi.org/10.1021/np800491u] [PMID: 19072214]
[http://dx.doi.org/10.1016/j.jsbmb.2007.03.028] [PMID: 17451940]
[http://dx.doi.org/10.1016/j.bmc.2004.10.058] [PMID: 15653333]
[http://dx.doi.org/10.1016/j.phytochem.2008.10.009] [PMID: 19062050]
[http://dx.doi.org/10.1016/j.ejmech.2014.11.039] [PMID: 25482554]
[http://dx.doi.org/10.1080/00397911.2014.894528]
[http://dx.doi.org/10.1039/a703305b]
[http://dx.doi.org/10.1021/jo961051a]
[http://dx.doi.org/10.1021/jo0623742] [PMID: 17286440]
[http://dx.doi.org/10.1016/j.tet.2011.12.042]
[http://dx.doi.org/10.1021/jo200485q] [PMID: 21480664]
[http://dx.doi.org/10.1016/j.tetlet.2012.08.078]
[http://dx.doi.org/10.3987/COM-02-S21]
[http://dx.doi.org/10.1016/j.tetlet.2013.03.040]
[http://dx.doi.org/10.1021/ol0272040] [PMID: 12489972]
[http://dx.doi.org/10.1016/j.tetlet.2003.09.080]
[http://dx.doi.org/10.1002/adsc.201301010]
[http://dx.doi.org/10.3762/bjoc.9.160] [PMID: 23946838]
[http://dx.doi.org/10.1039/c0ob01161d] [PMID: 21448470]
[http://dx.doi.org/10.1002/9780470711828.ch13]
[http://dx.doi.org/10.2174/13852728113179990018]
[http://dx.doi.org/10.1039/C6RA14228A]
[http://dx.doi.org/10.1038/nature06261] [PMID: 18046409]
[PMID: 14634227]
[http://dx.doi.org/10.1186/s12935-015-0196-y] [PMID: 26052253]
[http://dx.doi.org/10.1002/cmdc.200700003] [PMID: 17628866]
[http://dx.doi.org/10.1016/j.bmcl.2012.08.017] [PMID: 22929231]
[http://dx.doi.org/10.1016/S0092-8674(01)00524-4] [PMID: 11672522]
[http://dx.doi.org/10.1016/S0092-8674(01)00527-X] [PMID: 11672523]
[http://dx.doi.org/10.1016/0003-2697(76)90527-3] [PMID: 942051]
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]