Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 2 (VEGFR2) play an important role in cancer growth. Both of them have close relationships. Expression of EGFR will induce an angiogenic factor (VEGF) release for binding with VEGFR2. However, the existence of VEGF up-regulation independent of EGFR leads to cancer cell resistance to anti-EGFR. Therefore, a therapeutic approach targeting EGFR and VEGFR2 simultaneously may improve the outcome of cancer treatment. The present study was designed to identify potential compounds as a dual inhibitor of EGFR and VEGFR2 by the computational method. Firstly, the ligand-based pharmacophore model for each target was setup to screen of ZINC database of purchasable compounds. The hit compounds obtained by pharmacophore screening were then further screened by molecular docking studies. Taking erlotinib (EGFR inhibitor) and axitinib (VEGFR2 inhibitor) as reference drugs, six potential compounds (ZINC08398597, ZINC12047553, ZINC16525481, ZINC17418102, ZINC21942954, and ZINC38484632) were selected based on their docking scores and binding interaction. However, molecular dynamics simulations demonstrated that only ZINC16525481 and ZINC38484632 which have good binding free energy and stable hydrogen bonding interactions with EGFR and VEGFR2. The result represents a promising starting point for developing potent dual tyrosine kinases inhibitor of EGFR and VEGFR2.

Breast cancer (BC) is a multifactorial disease involving many pathways and target molecules. Multi-target therapy through multi-compound herbal medicines is an alternative strategy to treat BC. In the present study, we elucidate the molecular mechanism of Ocimum basilicum (OB) as an anticancer agent using system bioinformatic approach and investigate its cytotoxic effect against MCF-7 cells. We performed network pharmacology (NP) and molecular docking studies to provide scientific information regarding the underlying anti-BC mechanism of OB. Based on topology parameters obtained from protein-protein interaction (PPI), we identified six potential targets that play a significant role in the network including SRC, PI3KCA, EGFR, ESR1, AKT1, and MAPK1. Furthermore, consensus docking suggested rutin, quercetin-3-O-diglucoside, and kaempferol-3-O-β-D-rutinoside as the potential compounds of OB. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the cytotoxic effect of OB might be related to the modulation of several pathways such as PI3K-Akt, VEGF, and HIF-1, breast cancer, and estrogen signaling pathways. The in vitro assay revealed that various extracts of OB demonstrated cytotoxic effects against MCF-7 with IC₅₀ = 231 µg/mL (OB ethanolic extract), 408 µg/mL (OB methanolic extract), 479 µg/mL (OB ethyl acetate extract), 1887 µg/mL (OB n-hexanoic extract) and 767 µg/mL (OB butanolic extract) respectively.

Fern is one of the groups of primitive plants rich in secondary metabolites that are commonly used to treat various diseases, including antioxidant, anti-hyaluronidase, anti-inflammation, and respiratory disease but less investigated. Flavonoid is one of the secondary metabolites abundantly present in ferns. This study aims to isolate major compounds found in Blechnum orientale act as 15-lipoxygenase (15-LOX) inhibitors. Inhibition of lipoxygenase decrease the production of leukotriene that induces bronchoconstriction in asthma. Isoquercitrin (Quercetin-3-O-β-glucopyranoside) and trifolin (kaempferol-3-O-β-D-galactoside) have been successfully isolated from Blechnum orientale. Further in silico study was performed to explain the binding mode between flavonoid pyranoside or galactoside and flavonoid aglycone in the 15-LOX cavity and their amino acid residues interaction. Isoquercitrin binds with Ile663, Ile400, Leu408, Leu597, Ala404, and Arg403 in the 15-LOX cavity as a lipoxygenase inhibitor. Trifolin binds the same amino acids as isoquercetin with addition His366, Gln596, and Phe175. Both isoquercitrin and trifolin act as competitive inhibitors against lipoxygenase enzymes.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) requires finding new drugs or repurposing drugs for clinical use. Molecular docking belongs to structure-based drug design providing a fast method for identifying the hit compounds with antiviral activity against SARS-Cov-2. However, the weakness of the docking method is compounded by the limited crystallographic information and comparison drugs due to the novelty of this virus can present challenges in identifying hits of anti-SARS-Cov-2. In the current review, we highlighted several aspects, especially those related to the target structure, docking validation, and virtual hit selection, that need to be considered to obtain reliable docking results. Here, we discussed several cases pertaining to the issue highlighted and approaches that could be used to solve them.