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Synthesis, Antiproliferative and Pro-Apoptotic Effects of Nitrostyrenes and Related Compounds in Burkitt's Lymphoma.
Med Chem 2018; 14(2):181-199MC

Abstract

BACKGROUND

Cancers of the lymphatic cells (lymphomas) account for approximately 12% of malignant diseases worldwide. The nitrostyrene scaffold is identified as a lead target structure for the development of particularly effective compounds targeting Burkitt's lymphoma (BL).

OBJECTIVES

The aims of the curent study were to synthesise a panel of nitrostyrene compounds and to evaluate their activity in Burkitt's lymphoma (BL).

METHODS

A panel of structurally varied compounds were designed and synthesised using Henry Knoevenagel condensation reactions. Single crystal X-Ray analysis confirmed the E configuration for six examples of these novel structures. A number of nitrostyrene-related compounds were also investigated including 1,3-bis(aryl)-2-nitropropenes together with heterocyclic scaffolds containing the nitrovinyl pharmacophore such as 3-nitro-2-phenyl-2H-chromenes. The antiproliferative activities of the compounds were evaluated using the BL cell lines EBV- MUTU-1 and EBV+ DG- 75 (chemoresistant) to establish preliminary structure-activity relationships.

RESULTS

Lead compounds with optimized nitrostyrene scaffolds and 3-nitro-2-phenyl-2Hchromene structures were successfully established with typical IC50 values of 0.45 µM and 0.47 µM in MUTU-1 cells and 1.41 µM and 1.92 µM, respectively, in DG-75 cells. The mechanism of cell death was identified as apoptotic and the lead compound was found to elicit comparable apoptotic effects to Taxol in Burkitt's lymphoma cell lines MUTU-1 and DG-75.

CONCLUSION

This class of pharmaceutically active compounds with potential for the treatment of Burkitt`s lymphoma suggest a potential role for nitrostyrene based agents in chemotherapy.

Authors+Show Affiliations

School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse St, Dublin 2, Ireland.School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, 152-160 Pearse St, Dublin 2, Trinity College Dublin, Ireland.School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, 152-160 Pearse St, Dublin 2, Trinity College Dublin, Ireland.School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse St, Dublin 2, Ireland.School of Chemistry, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.School of Chemistry, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, 152-160 Pearse St, Dublin 2, Trinity College Dublin, Ireland.School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse St, Dublin 2, Ireland.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28969575

Citation

Byrne, Andrew J., et al. "Synthesis, Antiproliferative and Pro-Apoptotic Effects of Nitrostyrenes and Related Compounds in Burkitt's Lymphoma." Medicinal Chemistry (Shariqah (United Arab Emirates)), vol. 14, no. 2, 2018, pp. 181-199.
Byrne AJ, Bright SA, Fayne D, et al. Synthesis, Antiproliferative and Pro-Apoptotic Effects of Nitrostyrenes and Related Compounds in Burkitt's Lymphoma. Med Chem. 2018;14(2):181-199.
Byrne, A. J., Bright, S. A., Fayne, D., McKeown, J. P., McCabe, T., Twamley, B., ... Meegan, M. J. (2018). Synthesis, Antiproliferative and Pro-Apoptotic Effects of Nitrostyrenes and Related Compounds in Burkitt's Lymphoma. Medicinal Chemistry (Shariqah (United Arab Emirates)), 14(2), pp. 181-199. doi:10.2174/1573406413666171002123907.
Byrne AJ, et al. Synthesis, Antiproliferative and Pro-Apoptotic Effects of Nitrostyrenes and Related Compounds in Burkitt's Lymphoma. Med Chem. 2018 Feb 6;14(2):181-199. PubMed PMID: 28969575.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis, Antiproliferative and Pro-Apoptotic Effects of Nitrostyrenes and Related Compounds in Burkitt's Lymphoma. AU - Byrne,Andrew J, AU - Bright,Sandra A, AU - Fayne,Darren, AU - McKeown,James P, AU - McCabe,Thomas, AU - Twamley,Brendan, AU - Williams,Clive, AU - Meegan,Mary J, PY - 2017/01/12/received PY - 2017/08/03/revised PY - 2017/09/21/accepted PY - 2017/10/4/pubmed PY - 2018/3/6/medline PY - 2017/10/4/entrez KW - 3-Nitro-2-pheny-2H-chromene KW - Anticancer agent KW - B cell KW - Burkitt's lymphoma KW - DG-75 KW - MUTU-1 KW - nitrostyrene SP - 181 EP - 199 JF - Medicinal chemistry (Shariqah (United Arab Emirates)) JO - Med Chem VL - 14 IS - 2 N2 - BACKGROUND: Cancers of the lymphatic cells (lymphomas) account for approximately 12% of malignant diseases worldwide. The nitrostyrene scaffold is identified as a lead target structure for the development of particularly effective compounds targeting Burkitt's lymphoma (BL). OBJECTIVES: The aims of the curent study were to synthesise a panel of nitrostyrene compounds and to evaluate their activity in Burkitt's lymphoma (BL). METHODS: A panel of structurally varied compounds were designed and synthesised using Henry Knoevenagel condensation reactions. Single crystal X-Ray analysis confirmed the E configuration for six examples of these novel structures. A number of nitrostyrene-related compounds were also investigated including 1,3-bis(aryl)-2-nitropropenes together with heterocyclic scaffolds containing the nitrovinyl pharmacophore such as 3-nitro-2-phenyl-2H-chromenes. The antiproliferative activities of the compounds were evaluated using the BL cell lines EBV- MUTU-1 and EBV+ DG- 75 (chemoresistant) to establish preliminary structure-activity relationships. RESULTS: Lead compounds with optimized nitrostyrene scaffolds and 3-nitro-2-phenyl-2Hchromene structures were successfully established with typical IC50 values of 0.45 µM and 0.47 µM in MUTU-1 cells and 1.41 µM and 1.92 µM, respectively, in DG-75 cells. The mechanism of cell death was identified as apoptotic and the lead compound was found to elicit comparable apoptotic effects to Taxol in Burkitt's lymphoma cell lines MUTU-1 and DG-75. CONCLUSION: This class of pharmaceutically active compounds with potential for the treatment of Burkitt`s lymphoma suggest a potential role for nitrostyrene based agents in chemotherapy. SN - 1875-6638 UR - https://www.unboundmedicine.com/medline/citation/28969575/Synthesis_Antiproliferative_and_Pro_Apoptotic_Effects_of_Nitrostyrenes_and_Related_Compounds_in_Burkitt's_Lymphoma_ L2 - http://www.eurekaselect.com/156055/article DB - PRIME DP - Unbound Medicine ER -