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 ( E )-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 ( E )-9-chloro-10-(2-nitrobut-1-en-1-yl)anthracene ( 19f ) and the related 4-(anthracen-9-yl)-1 H -1,2,3-triazole ( 30a ). The ( E )-9-(2-nitrovinyl)anthracenes 19a, 19g and 19i-19m were found to elicit potent antiproliferative effects in both BL cell lines EBV - MUTU-1 (chemosensitive) and EBV + DG-75 (chemoresistant) with >90% inhibition at 10 μM. Selected ( E )-9-(2-nitrovinyl)anthracenes demonstrated potent antiproliferative activity in CLL cell lines, with IC 50 values of 0.17 μM (HG-3) and 1.3 μM (PGA-1) for compound 19g . The pro-apoptotic effects of the most potent compounds 19a , 19g , 19i , 19l and 19m were demonstrated in both CLL cell lines HG-3 and PGA-1. The ( E )-nitrostyrene and ( E )-9-(2-nitrovinyl)anthracene series of compounds offer potential for further development as novel chemotherapeutics for CLL.