Twenty-three　ursolic　acid　(1)　derivatives　2-24　(ten　novel　compounds　8-10,　14-17　and　22-24)　modified　at　the　C-3　and　the　C-28　positions　were　synthesized,　and　their　structures　were　confirmed　by　IR,　(1)H　NMR,　MS,　and　elemental　analysis.　The　single　crystals　of　compounds　15　and　17　were　obtained.　The　cytotoxic　activity　of　the　derivatives　was　evaluated　against　HepG2,　BGC-823,　SH-SY5Y,　HeLa　and　HELF　cells　by　the　MTT　assay.　The　induction　of　apoptosis　and　affects　on　the　cell　cycle　distribution　with　compound　14　were　assessed　by　fluorescence　microscopy,　flow　cytometry　and　the　activity　of　caspase-3　in　HepG2　cells.　Compounds　14-17　had　more　significant　antiproliferative　ability　against　the　four　cancer　cell　lines　and　low　cytotoxicity　to　human　embryonic　lung　fibroblast　cells　(HELF).　Compounds　11,　14-16,　21　and　23　were　particularly　active　against　HepG2　cell　growth.　Compound　14　was　selected　to　investigate　cell　apoptosis　and　cell　cycle　distribution.　Flow　cytometric　analysis　and　morphologic　changes　of　the　cell　exhibited　that　treatment　of　HepG2　cells　with　compound　14　led　to　cell　apoptosis　accompanied　by　cell　cycle　arrest　at　the　S　phase　in　a　dose-dependent　manner.　Furthermore,　the　activity　of　the　caspase-3　enzyme　was　increased　in　the　treated　cells.　In　vivo　studies　using　H22　xenografts　in　Kunming　mice　were　conducted　with　compound　14　at　doses　of　50,　100　and　150　mg/kg　body　weight　The　results　revealed　that　the　medium　dosage　group　(100　mg/kg)　showed　significant　anticancer　activity　(45.6　+/-　4.3%)　compared　to　the　control　group.　(C)　2011　Elsevier　Masson　SAS.　All　rights　reserved.