Physicochemical and Pharmacokinetic Analysis of Anacardic Acid Derivatives
2020
Anacardic acid (AA) and its derivatives are well-known for their
therapeutic applications ranging from antitumor, antibacterial, antioxidant,
anticancer, and so forth. However, their poor pharmacokinetic and
safety properties create significant hurdles in the formulation of
the final drug molecule. As a part of our endeavor to enhance the
potential and exploration of the anticancer activities, a detailed
study on the properties of selected AA derivatives was performed in
this work. A comprehensive analysis of the drug-like properties of
100 naturally occurring AA derivatives was performed, and the results
were compared with certain marketed anticancer drugs. The work focused
on the understanding of the interplay among eight physicochemical
properties. The relationships between the physicochemical properties,
absorption, distribution, metabolism, and excretion attributes, and
the in silico toxicity profile for the set of AA derivatives were
established. The ligand efficacy of the finally scrutinized 17 AA
derivatives on the basis of pharmacokinetic properties and toxicity
parameters was further subjected to dock against the potential anticancer
target cyclin-dependent kinase 2 (PDB ID: 1W98). In the docked complex, the ligand molecules
(AA derivatives) selectively bind with the target residues, and a
high binding affinity of the ligand molecules was ensured by the full
fitness score using the SwissDock Web server. The BOILED-Egg model
shows that out of 17 scrutinized molecules, 3 molecules exhibit gastrointestinal
absorption capability and 14 molecules exhibit permeability through
the blood–brain barrier penetration. The analysis can also
provide some useful insights to chemists to modify the existing natural
scaffolds in designing new anacardic anticancer drugs. The increased
probability of success may lead to the identification of drug-like
candidates with favorable safety profiles after further clinical evaluation.
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