Semi-Synthesis, Anti-Leukemia Activity, and Docking Study of Derivatives from 3,24-Dihydroxylup-20(29)-en-28-Oic Acid.

Current treatments against leukemia present several limitations, prompting the search for new therapeutic agents, particularly those derived from natural products. In this context, structural modifications were performed on the triterpene 3,24-dihydroxylup-20(29)-en-28-oic acid (), isolated from . Among the five derivatives obtained, 3,24-dihydroxy-30-oxolup-20(29)-en-28-oic acid () exhibited the highest activity, with an IC value of 12.90 ± 0.1 µM against THP-1 cells. significantly reduced cell viability in both acute lymphoblastic leukemia (CCRF-CEM, REH, JURKAT, and MOLT-4) and acute myeloid leukemia (THP-1) cell lines, inducing apoptosis after 48 h of treatment, while showing minimal cytotoxicity toward normal mononuclear cells (MNCs). In silico molecular docking studies were conducted against three key protein targets: BCL-2 (B-cell lymphoma 2), EGFR (epidermal growth factor receptor, tyrosine kinase domain), and FLT3 (FMS-like tyrosine kinase 3). The lowest binding energies (kcal/mol) observed were as follows: -BCL-2: -10.12, EGFR: -12.75, FLT3: -14.05; -BCL-2: -10.23, EGFR: -14.50, FLT3: -14.07; -BCL-2: -11.59, EGFR: -15.00, FLT3: -14.03. These findings highlight as a promising candidate in the search for anti-leukemic drugs which deserves further study.