Synthesis and antitumour evaluation of Monastrol and analogues

Cancer is a disease with a high incidence and mortality rate and is responsible for around 12 per cent of all deaths worldwide. For this reason, there is great interest in developing compounds with cytotoxic activity, especially with the aim of getting round the problem of resistance. The aim of this book was to synthesise six dihydropyrimidinones (DHPMs) and investigate their antitumour activity against a leukaemic cell line (U937). The compounds have hydroxyl groups in the ortho, meta and para positions of the benzene ring and oxygen or sulphur in the pyrimidine ring. After synthesising the compounds under thermal conditions and microwave irradiation, the DHPMs were evaluated for antitumour activity using the MTT metabolisation method. The sulphur portion in the structures of the DHPMs significantly increased the antitumour activity for the U937 leukaemia cell type. This was confirmed by the reduction in IC50 to 84 mimol.L-1. This study found that the position of the hydroxyl group in the benzene ring influences the antitumour activity observed for U937 leukaemia cells, showing that the hydroxyl group in the ortho position of the benzene ring is the most active.