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Open AccessArticle

Design, Synthesis and Biochemical Evaluation of Novel Ethanoanthracenes and Related Compounds to Target Burkitt’s Lymphoma

1
School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse St, Dublin 2, D02 R590, Ireland
2
School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse St, Dublin 2, D02 R590, Ireland
3
School of Chemistry, Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse St, Dublin 2, D02 R590, Ireland
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2020, 13(1), 16; https://doi.org/10.3390/ph13010016
Received: 19 December 2019 / Revised: 8 January 2020 / Accepted: 10 January 2020 / Published: 17 January 2020
Lymphomas (cancers of the lymphatic system) account for 12% of malignant diseases worldwide. Burkitt’s lymphoma (BL) is a rare form of non-Hodgkin’s lymphoma in which the cancer starts in the immune B-cells. We report the synthesis and preliminary studies on the antiproliferative activity of a library of 9,10-dihydro-9,10-ethanoanthracene based compounds structurally related to the antidepressant drug maprotiline against BL cell lines MUTU-1 and DG-75. Structural modifications were achieved by Diels-Alder reaction of the core 9-(2-nitrovinyl)anthracene with number of dienophiles including maleic anhydride, maleimides, acrylonitrile and benzyne. The antiproliferative activity of these compounds was evaluated in BL cell lines EBV MUTU-1 and EBV+ DG-75 (chemoresistant). The most potent compounds 13j, 15, 16a, 16b, 16c, 16d and 19a displayed IC50 values in the range 0.17–0.38 μM against the BL cell line EBV MUTU-1 and IC50 values in the range 0.45–0.78 μM against the chemoresistant BL cell line EBV+ DG-75. Compounds 15, 16b and 16c demonstrated potent ROS dependent apoptotic effects on the BL cell lines which were superior to the control drug taxol and showed minimal cytotoxicity to peripheral blood mononuclear cells (PBMCs). The results suggest that this class of compounds merits further investigation as antiproliferative agents for BL. View Full-Text
Keywords: Burkitt’s lymphoma; DG-75; MUTU-1; anthracene; nitrostyrene; maprotiline; 9,10-dihydro-9,10-ethanoanthracene; apoptosis Burkitt’s lymphoma; DG-75; MUTU-1; anthracene; nitrostyrene; maprotiline; 9,10-dihydro-9,10-ethanoanthracene; apoptosis
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MDPI and ACS Style

Byrne, A.J.; Bright, S.A.; McKeown, J.P.; O’Brien, J.E.; Twamley, B.; Fayne, D.; Williams, D.C.; Meegan, M.J. Design, Synthesis and Biochemical Evaluation of Novel Ethanoanthracenes and Related Compounds to Target Burkitt’s Lymphoma. Pharmaceuticals 2020, 13, 16.

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