biostudies-literatureGoncalves BMFUniversidade de CoimbraPrograma Operacional Regional do CentroEuropean Regional Development Fund313-331https://www.ebi.ac.uk/biostudies/studies/S-EPMC9945870biostudies-literatureUnknown14(2)Arjunolic acid (AA) is a pentacyclic triterpenoid with promising anticancer properties. A series of novel AA derivatives containing a pentameric A-ring with an enal moiety, combined with additional modifications at C-28, were designed and prepared. The biological activity on the viability of human cancer and non-tumor cell lines was evaluated in order to identify the most promising derivatives. Additionally, a preliminary study of the structure-activity relationship was carried out. The most active derivative, derivative 26, also showed the best selectivity between malignant cells and non-malignant fibroblasts. For compound 26, the anticancer molecular mechanism of action in PANC-1 cells was further studied and the results showed that this derivative induced a cell-cycle arrest at G0/G1 phRSC medicinal chemistryDesign, synthesis, and biological evaluation of new arjunolic acid derivatives as anticancer agents.PMC9945870CENTRO-01-0247-FEDER-003269Salvador JARGoncalves BMFSilvestre SMMendes VISfalseDesign, synthesis, and biological evaluation of new arjunolic acid derivatives as anticancer agents.Arjunolic acid (AA) is a pentacyclic triterpenoid with promising anticancer properties. A series of novel AA derivatives containing a pentameric A-ring with an enal moiety, combined with additional modifications at C-28, were designed and prepared. The biological activity on the viability of human cancer and non-tumor cell lines was evaluated in order to identify the most promising derivatives. Additionally, a preliminary study of the structure-activity relationship was carried out. The most active derivative, derivative 26, also showed the best selectivity between malignant cells and non-malignant fibroblasts. For compound 26, the anticancer molecular mechanism of action in PANC-1 cells was further studied and the results showed that this derivative induced a cell-cycle arrest at G0/G1 ph2023-01-01T00:00:00Z2023 Feb2026-03-18T14:08:16.32Z2025-08-23T03:09:06.433ZS-EPMC99458703684636210.1039/d2md00275b