Fig 1.
Schematic representation of the various processes used in the study.
Briefly, AML targets and modern drugs (small molecule drugs) were obtained from drug bank, therapeutic target database (TTD) and/or literatures sources. B. antidysentrica phytochemicals were compiled from Ethiopian traditional medicine database (ETM-DB) and/or literatures. Then, the modern drugs, phytochemicals and random compounds (obtained from PubChem) were docked with AML targets. Binding energies of small molecule drugs and phytochemicals were evaluated against that of random compounds with statistical test. Finally, the candidate therapeutic phytochemicals were selected based on the statistical analysis and cutoff binding energies. In addition, the candidate compounds were further evaluated for drug-likeness, physicochemical and ADMET properties.
Fig 2.
2D structures of the investigated compounds in this study.
(A) Selected B. antidysentrica phytochemicals and (B) Small molecule drugs.
Fig 3.
Scatter plots of the docking scores of compound-target interactions for each AML therapeutic targets.
(A) compound—target docking score visualization for each AML targets, (B) compound—target docking scores combined for all the four AML targets.
Fig 4.
Molecular docking analysis of enasidenib and selected B. antidysentrica phytochemicals against IDH2 AML receptor.
(1) 3D pose views of interaction of compounds with AML receptor IDH2. (2) 2D pose views of interaction of compounds with AML receptor IDH2.
Fig 5.
Molecular docking analysis of AMG176 and selected B. antidysentrica phytochemicals against MCL1 AML receptor.
(1) 3D pose views of interaction of compounds with AML receptor MCL1. (2) 2D pose views of interaction of compounds with AML receptor MCL1.
Fig 6.
Molecular docking analysis of gilteritinib and selected B. antidysentrica phytochemicals against FLT3 AML receptor.
(1) 3D pose views of interaction of compounds with AML receptor FLT3. (2) 2D pose views of interaction of compounds with AML receptor FLT3.
Fig 7.
Molecular docking analysis of venetoclax and selected B. antidysentrica phytochemicals against BCL2 AML receptor.
(1) 3D pose views of interaction of compounds with AML receptor FLT3. (2) 2D pose views of interaction of compounds with AML receptor BCL2.
Table 1.
Binding affinity energies, nature of interaction and interacting amino acid residues between the compounds (small molecule drug and phytochemicals) and AML receptors.
Table 2.
Lipinski’s rule of five and Veber’s rule for drug-likeness analysis of selected phytochemicals and small molecule drugs.
Table 3.
Calculated physicochemical properties and toxicity class of selected B. antidysentrica phytochemicals and small molecule drugs.
Fig 8.
BOILED-Egg model of small molecule standard drugs and selected B. antidysentrica phytochemicals.
Table 4.
Interaction of selected B. antidysentrica phytochemicals and small molecule modern drugs with P-glycoprotein and cytochrome P450 isoenzymes.