Evaluation of antileukemic potentials of maslinic acid through targeting responsive proteins of human leukemia: a mechanistic perception on molecular modelling and dynamic stimulations

通过靶向人类白血病反应蛋白评估马斯林酸的抗白血病潜力:基于分子建模和动态刺激的机制性认识

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Abstract

Maslinic acid (MA), a plant-derived pentacyclic triterpene, was compared to the FDA-approved drugs dasatinib (DAS) and doxorubicin (DOX) to determine its antileukemic potential. Chronic Myeloid Leukaemia and Acute Myeloid Leukaemia were caused by mutations in the BCR-ABL kinase which is regulated by CBL-kinase and FLT3 over the decade. This present investigation aimed to identify the antileukemic potential of MA as compared to the FDA-approved drugs dasatinib (DAS) and doxorubicin (DOX) via an in silico approach. MA had strong binding affinity with leukemic target proteins, with similar affinity and stability to DAS and DOX. Pharmacokinetic and toxicology studies revealed that MA has drug-like characteristics and a lower toxicity profile (LD50: 205 mg/kg). MD simulations during a 100 ns period revealed that MA obtained stable binding conformations, with RMSD, RMSF, Rg, and hydrogen bonding evaluations indicating performance comparable to the reference medicines. Thus, these results illustrate that MA may act as a natural scaffold with antileukemic properties and call for additional experimental confirmation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-025-00478-3.

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