biostudies-literatureUnknown10Shu YWith the purpose to improve antiproliferative activity, 26 new betulonic acid-diazine derivatives were designed and synthesized from betulinic acid. The anticancer activity of these semi-synthetic compounds was evaluated by MTT assay in both tumor cell lines and normal cell line. The results indicated that majority of new compounds exhibited improved antitumor activity compared with the parent compound betulonic acid. Compound <b>BoA2C</b>, in particular, had the most significant action with IC₅₀ value of 3.39 μM against MCF-7 cells, while it showed lower cytotoxicity on MDCK cell line than cisplatin. Furthermore, we discovered that <b>BoA2C</b> strongly increased MCF-7 cell damage mostly by influencing arginine and fatty acid metabolism. In addition, the structure-activity relaFrontiers in chemistry969770https://www.ebi.ac.uk/biostudies/studies/S-EPMC9486541biostudies-literatureDesign, synthesis and cytotoxic evaluation of novel betulonic acid-diazine derivatives as potential antitumor agents.PMC9486541Yan MMa QDing XWang PZhang YLei HLi FHan YLiang MShu YGao FfalseDesign, synthesis and cytotoxic evaluation of novel betulonic acid-diazine derivatives as potential antitumor agents.With the purpose to improve antiproliferative activity, 26 new betulonic acid-diazine derivatives were designed and synthesized from betulinic acid. The anticancer activity of these semi-synthetic compounds was evaluated by MTT assay in both tumor cell lines and normal cell line. The results indicated that majority of new compounds exhibited improved antitumor activity compared with the parent compound betulonic acid. Compound <b>BoA2C</b>, in particular, had the most significant action with IC₅₀ value of 3.39 μM against MCF-7 cells, while it showed lower cytotoxicity on MDCK cell line than cisplatin. Furthermore, we discovered that <b>BoA2C</b> strongly increased MCF-7 cell damage mostly by influencing arginine and fatty acid metabolism. In addition, the structure-activity rela2022-01-01T00:00:00Z20222025-04-19T21:43:13.422Z2025-04-19T21:43:13.422ZS-EPMC94865413614725110.3389/fchem.2022.969770