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Synthesis, Molecular Docking, and DFT Calculation of a Half‐Strapped BODIPY as Potential EGFR Inhibitor **
Author(s) -
Parveen Shazia,
Alnoman Rua B.,
Hagar Mohamad,
Ahmed Hoda A.,
Knight Julian G.
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202003621
Subject(s) - adme , chemistry , lipophilicity , docking (animal) , molecular orbital , epidermal growth factor receptor , stereochemistry , biochemistry , in vitro , molecule , receptor , organic chemistry , medicine , nursing
The identification of drug candidates inhibiting specific cellular functions in cancer cell progression is reflected as a key in cancer treatment. The overexpression of epidermal growth factor receptor, EGFR is witnessed in a huge number of cancers. Hence targeting the EGFR and its downstream signaling cascades are considered as a coherent approach in cancer therapy. Keeping this in view, we have synthesized six 4,4‐Difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene/boron‐dipyrromethene (BODIPY) compounds, 1 – 6 . Absorption, distribution, metabolism and excretion (ADME) and Lipinski's drug likeness of compounds 1 – 6 was predicted revealing that they exhibited promising physicochemical properties for oral bioavailability. Molecular docking results revealed that compound 6 displayed highest lipophilicity, hence strongest binding to the protein (ΔG=−8.78 kcal/mol) as compared to compounds 4 and 5 . The density functional calculations have been investigated to validate the evidence about the reactivity of the compounds as inhibitors. These results were illustrated in terms of the chemical reactivity descriptors and the molecular electrostatic potential (MEP). Compound 6 showed the highest lying HOMO (highest occupied molecular orbital), the smallest energy gap between the FMOs (Frontier molecular orbitals) and the lowest basicity index, all of these parameters could affect the binding affinity, to different extents, to impact the degree of the binding of compound 6 with the active protein sites.