Structure-based design, synthesis and biological evaluation of new small molecules anti-cancer agents were described. On continuation of applying scaffold hopping theory, a series of 5-arylthieno[2,3-d]pyrimidines based on the structural features of lapatinib was designed, synthesized and characterized using IR, H-1-NMR, C-13-NMR, mass and microanalyses. Biological evaluation of the cytotoxic activity against MCF-7 cell line and the inhibition of the enzymatic activity of epidermal growth factor tyrosine kinase were carried out in vitro for the target compounds. Substituting the 4-anilino-5-arylthieno[2,3-d]pyrimidines with different pharmacophoric groups at ortho, meta and/or para positions led to discovery of two potent lead compounds 3b and f with excellent cytotoxic activity and enzymatic inhibition activity.

A crucial target in drug research is magnifying efficacy and decreasing toxicity. Therefore, using natural active constituents as precursors will enhance both safety and biological activities. Despite having many pharmacological activities, caffeic and ferulic acids showed limited clinical usage due to their poor bioavailability and fast elimination. Therefore, semisynthetic compounds from these two acids were prepared and screened as anticancer agents. In this study, CA and FA showed very potent anticancer activity against Caco-2 cells. Consequently, eighteen derivatives were tested against the same cell line. Four potent candidates were selected for determination of the selectivity index, where compound 10 revealed a high safety margin. Compound 10 represented a new scaffold and showed significant cytotoxic activity against Caco-2. Cell-cycle analysis and evaluation of apoptosis showed that derivatives 10, 7, 11, 15 and 14 showed the highest proportion of cells in a late apoptotic stage.