Synthesis and Pro-Apoptotic Effects of Nitrovinylanthracenes and Related Compounds in Chronic Lymphocytic Leukaemia (CLL) and Burkitt's Lymphoma (BL).

Chronic lymphocytic leukaemia (CLL) is a malignancy of the immune B lymphocyte cells and is the most common leukaemia diagnosed in developed countries. In this paper, we report the synthesis and antiproliferative effects of a series of ()-9-(2-nitrovinyl)anthracenes and related nitrostyrene compounds in CLL cell lines and also in Burkitt's lymphoma (BL) cell lines, a rare form of non-Hodgkin's immune B-cell lymphoma. The nitrostyrene scaffold was identified as a lead structure for the development of effective compounds targeting BL and CLL. The series of structurally diverse nitrostyrenes was synthesised via Henry-Knoevenagel condensation reactions. Single-crystal X-ray analysis confirmed the structure of ()-9-chloro-10-(2-nitrobut-1-en-1-yl)anthracene () and the related 4-(anthracen-9-yl)-1-1,2,3-triazole (). The ()-9-(2-nitrovinyl)anthracenes and were found to elicit potent antiproliferative effects in both BL cell lines EBVMUTU-1 (chemosensitive) and EBV DG-75 (chemoresistant) with >90% inhibition at 10 μM. Selected ()-9-(2-nitrovinyl)anthracenes demonstrated potent antiproliferative activity in CLL cell lines, with IC values of 0.17 μM (HG-3) and 1.3 μM (PGA-1) for compound . The pro-apoptotic effects of the most potent compounds , , , and were demonstrated in both CLL cell lines HG-3 and PGA-1. The ()-nitrostyrene and ()-9-(2-nitrovinyl)anthracene series of compounds offer potential for further development as novel chemotherapeutics for CLL.