Ursolic　acid　(UA)　as　the　leader　compound　was　designed　to　prepare　a　series　of　derivatives　(three　novel　compounds　UA-1a,　UA-1b　and　UA-2)　by　modification　at　the　C3　and　C28　positions.　Their　chemical　structures　were　confirmed　by　IR,　1H　NMR　and　MS.　The　cytotoxic　activity　of　the　derivatives　was　evaluated　against　HepG2,　BGC-823　and　HT-29　by　the　MTT　assay.　The　novel　derivative　UA-1a,　[3β-acetoxy-urs-12-en-28-oyl]-1-monoglyceride　showed　significant　anti-growth　ability　against　the　assayed　cancer　cell　lines,　particularly　against　BGC-823,　while　low　cytotoxicity　to　human　normal　gastric　cell　line　GES-1.　Further　investigation　revealed　that　UA-1a　could　induce　apoptotic　events　of　the　treated　BGC-823　cells,　such　as　comet-like　DNA　bend,　sub-G0/G1　phase　accumulation　and　phosphatidylserine　externalization.　The　activity　of　Caspase-3　was　found　to　be　up-regulated,　while　the　expression　of　Bcl-2　and　Survivin　were　down-regulated　in　UA-1a　treated　cells.　UA-1a　might　trigger　the　death　of　BGC-823　cells　by　inducing　apoptosis　via　the　mitochondria　pathway.　UA-1a　exerted　stronger　ability　than　Taxol　to　retard　tumor　growth　in　nude　mice　without　leaving　apparent　toxicity　to　the　hosts.　The　experimental　data　suggested　that　UA-1a　would　have　a　therapeutic　potential　in　the　treatment　of　gastric　cancer.　©　2011　Elsevier　Ltd.　All　rights　reserved.