Natural and Semisynthetic Pentacyclic Triterpenes for Chronic Myeloid Leukemia Therapy: Reality, Challenges and Perspectives.

Renz Barreto Vianna, Débora; Gotardi, Jessica; Gnoatto, Simone Cristina Baggio; Pilger, Diogo André

Chronic myeloid leukemia (CML) is a neoplasm characterized by BCR-ABL1, an oncoprotein with vital role in leukemogenesis. Its inhibition by tyrosine kinase inhibitors represents the main choice of treatment. However, therapeutic failure is worrying given the lack of pharmacological options. Pentacyclic triterpenes are phytochemicals with outstanding antitumoral properties and have also been explored as a basis for the design of potential leads. In this review, we gathered and discussed data regarding both natural and semisynthetic pentacyclic triterpenes applied to CML cell treatment. We found consistent evidence that the class of pentacyclic triterpenes in general exerts promising pro-apoptotic and antiproliferative activities in sensitive and resistant CML cells, representing a rich source towards drug development. We also analyzed predicted drug-like properties of the molecules, discussed the structural changes with biological implications and showed the great opportunities this class represents, as well as the perspectives they provide to drug discovery for CML treatment.