Structural　modification　was　performed　at　the　C-3　and　C-28　positions　of　ursolic　acid　(UA).　Ten　UA　derivatives　with　distinct　electrical　property　were　synthesized.　They　could　be　divided　into　two　groups　according　to　their　charge　under　physiological　conditions:　(1)　Group　I　negatively　charged　and　(2)　Group　II　positively　charged.　The　anti-proliferative　capability　of　the　derivatives　was　evaluated　against　HepG2,　AGS,　HT-29　and　PC-3　cells　by　the　MTT　assay.　Flow　cytometry　and　Annexin　V/PI　dual　staining　assay　were　carried　out　to　explore　the　antitumor　mechanism.　The　results　showed　the　cytotoxic　capacity　of　the　compounds　was:　Group　I　＜　UA　＜　Group　II.　The　UA　derivatives　in　Group　II　exhibited　potent　cytotoxicity　and　the　enhancement　of　the　lipophilicity　could　further　strengthen　the　cytotoxicity.　Triggering　apoptosis　and　causing　cell　cycle　arrest　contributed　to　the　anticancer　mechanism.　The　UA　derivative　UA-7　had　the　therapeutic　potential　in　the　treatment　of　gastric　carcinoma　since　it　showed　potent　cytotoxicity,　reasonable　oil/water　partition,　enhanced　water　solubility,　and　the　ability　to　induce　the　apoptosis　of　AGS　cells.　©　2011　Elsevier　Ltd.　All　rights　reserved.