Synthesis of Analogues of Natural Product ‘Antheminone A’ and Evaluation of Their Anti-Cancer Activity

Abstract

Synthesis of two novel compounds (1a and 1b) derived from analogue of antheminone A (1c) and their evaluation of anti-cancer activities are hereby described. This synthesis involved a multi-step reaction sequence involving the use of natural product (-)-quinic acid (1d) and unsymmetrical dicoumarol (1e) as precursors (Figure 1). Unsymmetrical dicoumarol (1e), a potent inhibitor of NQO1 was synthesized by coupling 4-hydroxyl coumarin and an appropriate benzaldehyde. Thus, in order to facilitate drug penetration through the barriers of cell membrane to NQO1 location, compound (1e) was re-modified by coupling with an analogue of antheminone A (1c). Spectral analyses of the products were carried out in order to confirm the identity of the compounds. Interestingly, the compounds which were obtained in good to moderate yield (51-68%) exhibited toxicity against the non-small cancer cell line, A549.