Synthesis of new selective cytotoxic ricinine analogues against oral squamous cell carcinoma

Abstract

Sixteen new analogues were synthesized from ricinine and tested alongside with seven known analogues for their cytotoxic activity against oral cancer (SAS cells) and normal epithelial cells (L132 cells). In contrast to 5-FU, the synthesized ricinine analogues did not show toxicity to normal cells. However, some of them inhibited the proliferation of oral cancer cells at 25 µM as evident from the MTT assay results. Ricinine analogue (<b>19</b>) was shown to be the most active derivative (69.22% inhibition). Potential targets involved in the oral cancer inhibitory activity of compound <b>19</b> were investigated using <i>in-silico</i> studies and western blot analysis. PTP1B was predicted to be a target for ricinine using reverse docking approach. This prediction was confirmed by western blot analysis that revealed the downregulation of PTP1B protein by compound <b>19</b>. Moreover, it showed downregulation of COX-2 which is also extensively expressed in oral cancer.