Expanding the chemical space: Discovery of new anticancer 3-arylbenzofuran derivatives |
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| Authors: | Jinhwang Kim Hyeon-Min Cha Mikyung Park Dileep K. Singh Gi H. Bae Seong H. Kim Ikyon Kim |
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| Affiliation: | 1. College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, South Korea;2. Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, South Korea;3. Innovative Target Research Center, Therapeutics & Biotechnology Division, Korea Research Institute of Chemical Technology, Daejeon, South Korea |
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| Abstract: | A new chemical space was generated via C2-functionalization of 3-arylbenzofurans. Mannich reaction of 3-arylbenzofurans with secondary amines and formaldehyde allowed for installation of aminomethyl unit at C2 position of benzofurans. A formyl group at C2 site introduced as a result of Vilsmeier-Haack formylation of 3-arylbenzofurans was employed as a reacting partner for three-component Kabachnik-Fields reaction with various amines and triethyl phosphite to give a wide variety of aminomethylphosphonates. Furthermore, several benzo[d]oxazoles and pyrrolo[1,2-a]quinoxalines were prepared by using the formyl group. Biological screening of the synthesized compounds revealed that the benzofuran bearing a pyrrolo[1,2-a]quinoxaline moiety ( 5b ) most potently inhibited the viability of human blood cancer cells, but not solid tumor cells. Caspase activity assay, analysis of Annexin V-positive cells, and Western blot analysis indicated that 5b -induced death of human lymphoma U937 cells could result from its potential to induce the caspase-dependent apoptotic death of blood cancer cells with inhibition of ERK activation. |
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