The Anti-leukemic Activities of Campesterol and Α-Tocopherol Against BCL-2 Target through Computational Drug Design Approaches.

Abstract

Introduction: Heterogeneous Acute Myeloid Leukemia (AML) causes substantial worldwide morbidity and death. AML is characterized by excessive proliferation of immature myeloid cells in the bone marrow and impaired apoptotic regulator expression. B-Cell Lymphoma 2 (BCL-2), an anti-apoptotic protein overexpressed in AML, promotes leukemic cell survival and chemoresistance. Thus, reducing BCL-2 may treat AML. Anticancer activities are found in Aloe barbadensis Miller (Aloe vera). Thus, this work used molecular modeling to assess Aloe vera bioactive chemicals as BCL-2 inhibitors.

Methods: Selected bioactive compounds from Aloe vera was docked against BCL-2 using Auto- Dock Vina. drug-likeness, pharmacokinetics, and toxicity profiling was carried out using SwissAdme and ADMETSar servers. Finally, the two most promising compounds were subjected to 100 ns molecular dynamics (MD) simulation in Desmond software.

Results: The Binding energies of the compounds were found to be between -6.7 to -8.7 kcal/mol, with campesterol and a-tocopherol returning the least binding energy. Furthermore, both compounds displayed good druglikeness, and ADMET profiles. In addition, they maintained stable nature in the binding pocket of BCL-2 during the 100 ns MD simulation.

Conclusion: Campesterol and α-tocopherol are promising BCL-2 inhibitors that might become effective anti-leukemic therapies with additional in vitro and in vivo research.