Scientific publications
Mc Jésus Kinyok
Marius Balemaken Missi
Joseph Thierry Ndongo
Mune Mune Martin Alain
Other affiliations: University of Maroua
Dieudonné Emmanuel Pegnyemb
Mamoudou Hamadou* (Corresponding author)
Albert Fouda Atangana
Jairus Olumasai Nandwa
Gaétan Bayiha Ba Njock* (Corresponding author)
Jean Noël Nyemb
Current Proteomics
Resistance to current anticancer therapies drives the demand for novel, multitarget agents with improved safety. We screened flavonoid-derived phytochemicals isolated from Rhabdophyllum arnoldianum for inhibition of two cancer-relevant enzymes, tyrosine kinase (TK, PDB 1IRK) and dihydrofolate reductase (DHFR, PDB 1DYR). After retrieval from PubChem, the ligands were energy-minimised (MMFF94) and docked using two independent pipelines: (i) a stand-alone AutoDock Vina (v1.5.7) run and (ii) an autonomous PyRx (v0.8) workflow that also employs the Vina scoring function but generates its own grid and ligand-pre-processing. The two campaigns are highly concordant (Pearson r = 0.9759 for TK and r = 0.9816 for DHFR), confirming the robustness of the predicted binding affinities. A stringent consensus filter, requiring a compound to rank within the top 5 % of binding energies for both targets and in both pipelines, identified three reliable multitarget hits: 6″-α-Rhamnopyranosyl-7-O-methylvitexin ( 2 ), Rhusflavone ( 10 ), and Amentoflavone ( 11 ). All three display predicted free-energy values ≤ –8.3 kcal.mol⁻¹ for TK and ≤ –9.4 kcal.mol⁻¹ for DHFR, with virtually identical binding poses (RMSD ≤ 1.2 Å) across the two docking engines. Detailed inspection of the complexes reveals conserved interactions, hydrogen bonds to Lys-212 (TK) or Asp-27 (DHFR), π-π stacking with Phe-345 (TK) or Arg-70 (DHFR), and extensive hydrophobic contacts that occupy the ATP- and folate-binding pockets. In silico ADMET profiling indicates moderate oral bioavailability, acceptable intestinal absorption, low blood-brain-barrier permeation, and no overt cardiotoxic or hepatotoxic alerts, although Amentoflavone may inhibit CYP2D6. The cross-validated docking workflow thus provides a high-confidence shortlist of natural-product-derived, dual-TK/DHFR inhibitors, illustrating how tandem computational pipelines can accelerate the discovery of multitarget anticancer leads from medicinal plants.
