Semi-Synthesis, Anti-Leukemia Activity, and Docking Study of Derivatives from 3α,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 3α,24-dihydroxylup-20(29)-en-28-oic acid (T1), isolated from Phoradendron wattii. Among the five derivatives obtained, 3α,24-dihydroxy-30-oxolup-20(29)-en-28-oic acid (T1c) exhibited the highest activity, with an IC50 value of 12.90 ± 0.1 µM against THP-1 cells. T1c 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: T1-BCL-2: -10.12, EGFR: -12.75, FLT3: -14.05; T1c-BCL-2: -10.23, EGFR: -14.50, FLT3: -14.07; T2-BCL-2: -11.59, EGFR: -15.00, FLT3: -14.03. These findings highlight T1c as a promising candidate in the search for anti-leukemic drugs which deserves further study.