Ethanoanthracenes: Potential chemotherapeutics for chronic lymphocytic leukaemia (CLL)

Abstract

Chronic lymphocytic leukaemia (CLL) is the most commonly diagnosed leukaemia in the Western world, with an average age of diagnosis being over 65 years 1, 2. Despite development of new targeted therapeutics; emerging resistance, pharmacoeconomic sustainability and side-effect intolerability remain significant barriers to patient care and potential disease curability Chemical Synthesis Scheme & Figure 1: Synthesis of ethanoanthracene-based analogues with α,β-unsaturated carbonyl motif (blue) via a two-step process involving Claisen Schmidt condensation followed by Diels Alder cycloaddition onto tricyclic anthracene core (red) to create ethanoanthracene derivatives. The tail groups (purple) and head groups (green) used are outlined above. Biochemical Evaluation & SAR Elucidation Prior research with 2-nitrovinylanthracenes showed strong anti-proliferative proapoptototic activity in CLL lines (Fig. 2): PGA-1 (mutated Ig VH; good prognosis) and HG-3 (unmutated Ig VH; poor prognosis).