Pharmacophore-Based Virtual Screening and In-Silico Explorations of Biomolecules (Curcumin Derivatives) of

The newly FDA-approved drug, Axitinib, is an effective therapy against RTKs, but it possesses severe adverse effects like hypertension, stomatitis, and dose-dependent toxicity. In order to ameliorate Axitinib's downsides, the current study is expedited to search for energetically stable and optimized pharmacophore features of 14 curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione) derivatives. The rationale behind the selection of curcumin derivatives is their reported anti-angiogenic and anti-cancer properties. Furthermore, they possessed a low molecular weight and a low toxicity profile. In the current investigation, the pharmacophore model-based drug design, facilitates the filtering of curcumin derivatives as VEGFR2 interfacial inhibitors. Initially, the Axitinib scaffold was used to build a pharmacophore query model against which curcumin derivatives were screened. Then, top hits from pharmacophore virtual screening were subjected to in-depth computational studies such as molecular docking, density functional theory (DFT) studies, molecular dynamics (MD) simulations, and ADMET property prediction. The findings of the current investigation revealed the substantial chemical reactivity of the compounds. Specifically, compounds