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.