Synthesis and Antiproliferative Evaluation of 2-Deoxy-N-glycosylbenzotriazoles/imidazoles |
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| Authors: | Caleigh S. Garton Noelle K. DeRose Dylan Dominguez Maria L. Turbi-Henderson Ashley L. Lehr Ashley D. Padilla Scott D. Twining Stephanie Casas Chidozie O. Alozie Azad L. Gucwa Mohammed R. Elshaer Michael De Castro |
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| Affiliation: | 1.Department of Chemistry, Farmingdale State College-SUNY, 2350 Broadhollow Rd, Farmingdale, NY 11735, USA; (C.S.G.); (N.K.D.); (D.D.); (A.L.L.); (S.D.T.); (S.C.); (C.O.A.);2.Department of Biology, Farmingdale State College-SUNY, 2350 Broadhollow Rd, Farmingdale, NY 11735, USA; (M.L.T.-H.); (A.D.P.); (A.L.G.);3.Department of Chemistry, Biochemistry and Physics, Fairleigh Dickinson University, Madison, NJ 07940, USA |
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| Abstract: | A series of 2-deoxy-2-iodo-α-d-mannopyranosylbenzotriazoles was synthesized using the benzyl, 4,6-benzylidene and acetyl protected D-glucal in the presence of N-iodosuccinimide (NIS). Subsequent removal of the iodine at the C-2 position using tributyltin hydride under free radical conditions afforded the 2-deoxy-α-d-glucopyranosylbenzotriazoles in moderate to high yields. This method was extended to the preparation of substituted 2-deoxy-β-d-glucopyranosylimidazoles as well. The stereoselectivity of the addition reaction and the effect of the protecting group and temperature on anomer distribution of the benzotriazole series were also investigated. The anticancer properties of the newly synthesized compounds were evaluated in a series of viability studies using HeLa (human cervical adenocarcinoma), human breast and lung cancer cell lines. The N-[3,4,6-tri-O-benzyl-2-deoxy-α-d-glucopyranosyl]-1H-benzotriazole and the N-[3,4,6-tri-O-acetyl-2-deoxy-α-d-glucopyranosyl]-2H-benzotriazole were found to be the most potent cancer cell inhibitors at 20 µM concentrations across all four cell lines. |
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| Keywords: | benzotriazole D-glucal cytotoxic activity stereochemistry heterocycles |
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