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

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.

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.

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.

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