187585-43-9Relevant articles and documents
Synthesis, antiproliferative and pro-apoptotic effects of nitrostyrenes and related compounds in Burkitt’s lymphoma
Byrne, Andrew J.,Bright, Sandra A.,Fayne, Darren,McKeown, James P.,McCabe, Thomas,Twamley, Brendan,Williams, Clive,Meegan, Mary J.
, p. 181 - 199 (2018/03/13)
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.
Synthesis and in vitro cytotoxicity of a series of 3-aminoflavones
Dauzonne,Folleas,Martinez,Chabot
, p. 71 - 82 (2007/10/03)
To further understand the molecular requirements for the antiproliferative activity of flavonoids, a series of 3-aminoflavones and some of their derivatives were prepared and evaluated using L1210 murine leukemia. Our novel five-step synthetic approach required easily available substituted aromatic aldehydes as starting materials and proved more convenient and more general than previously reported methods. Our results in the 3-aminoflavones series indicated that the 4'-methoxy group is important for cytotoxic activity. Moreover, for the flavone-8-acetic analogs, a marked increase in potency was observed with the addition of a 3-amino or a 3-nitro group. Methoxy groups on the 6 and 7 positions of flavonoids (as in cirsiliol) also appear to be important for antiproliferative activity. These results are essential for the further understanding of the critical molecular requirements that lead to antiproliferative properties in the flavonoid series.