Design, synthesis and biological evaluation of asiatic acid derivatives as survivin inhibitors

Targeting Survivin with small molecules is a validated oncological strategy. Fourteen novel asiatic acid (AA) derivatives incorporating phosphate ester pharmacophores were designed and synthesized guided by the principles of fragment-based drug discovery and informed by the essential pharmacophoric features of known potent Survivin inhibitors. In vitro evaluation revealed that these compounds, particularly compound II₆, effectively inhibited the proliferation of MCF-7, A549 and HeLa cells. Molecular docking indicated that the designed compounds interact with key residues of Survivin through covalent and non-covalent interactions. The selected compound may suppress tumor proliferation via Survivin inhibition, constituting a potential lead for cancer therapy.