Galangal Rhizomes Phytoconstituents as VEGFR2 Inhibitors in Breast Cancer: Computational studies
DOI:
https://doi.org/10.24002/biota.v11i3.12790Keywords:
Breast cancer, Galangal, Molecular docking, In silico, VEGFR2Abstract
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women in Indonesia. Vascular endothelial growth factor receptor 2 (VEGFR-2), a key regulator of tumour angiogenesis, is an established therapeutic target, but existing inhibitors are costly and poorly tolerated. This study evaluated ten compounds reported from Kaempferia galanga rhizomes as potential VEGFR-2 inhibitors using in silico approaches, including Lipinski’s Rule of Five, ADMET prediction with PreADMET, pharmacophore screening with LigandScout, and molecular docking against VEGFR-2 (PDB ID: 3VO3). All ten compounds satisfied the Rule of Five. The selected pharmacophore model (Model 4, AUC = 0.78) retrieved eight of them as hits. Redocking of the native imidazo[1,2-b]pyridazine ligand gave an RMSD of 1.29 Å, a binding energy of -10.81 kcal/mol and a Ki of 11.93 nM, validating the protocol. Sandaracopimaradien-6β,9α-diol-1-one gave the lowest binding energy among the test compounds (-9.23 kcal/mol; Ki 172.53 nM) but formed no hydrogen bonds and failed the pharmacophore filter. Seven phenolic compounds reproduced the native ligand’s hydrogen bond to Glu885. Taking drug-likeness, predicted toxicity, pharmacophore fit and binding mode together, methyl (2R,3S)-2,3-dihydroxy-3-(4-methoxyphenyl)propanoate was the most promising VEGFR-2 inhibitor candidate, and confirmation by in vitro and in vivo testing is required.
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