Enhancement of antiproliferative activity by molecular simplification of catalpol

Molecular simplification of any given natural or synthetic template helps medicinal chemists designing shorten synthetic routes while keeping or enhancing the biological activity. This strategy is exemplified with simplified analogs of naturally occurring catalpol. Two iridoid scaffolds were synthesized enantioselectively using as key step an l-proline-catalyzed α-formyl oxidation. The in vitro antiproliferative activities were evaluated against a representative panel of human solid tumor cell lines. Both iridoids induced considerably growth inhibition in the range 0.38–1.86μM. Cell cycle studies for these compounds showed the induction of cell cycle arrest at the G1 phase. This result was consistent with a decrease in the expression of cyclin D1. Damaged cells underwent apoptosis as indicated by specific Annexin V staining.