Structure Based Drug Design of Shikimic Acid as a Putative Drug Target for BRCA via Insilico Method

Abstract
Cancer is a type of tumor that exhibits aberrant cell proliferation and
has the capacity to infiltrate or spread from its original organ (the
"site") to other body parts. Breast cancer is heterogenous disease
which may due to both genetic and environmental factors. Breast
cancer accounts for 23% of all cancer fatalities in postmenopausal
women, making it one of the top causes of death in this population.
The "shikimate pathway," also referred to as the "shikimic acid
pathway," is a metabolic route comprising seven steps, employed by
a range of organisms such as plants, bacteria, algae, fungi, and some
protozoans, for the biosynthesis of folates and aromatic amino acids.
Molecular docking simulations were performed to investigate the
binding interactions between shikimic acid and the target proteins
BRCA1 and BRCA2, and the resulting interactions, such as hydrogen
bonds, hydrophobic contacts, and electrostatic forces, were analyzed.
Docking studies of shikimic acid and Niraparib with BRCA1 and
BRCA2 were performed, considering the Lipinski rule, rerank score,
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Concepts and Statistical Approaches (2025)
and MolDock score. In vitro experiments – DPPH free-radical
scavenging and nitric oxide radical inhibition assays – were also
carried out to connect these findings with anticancer potency. The
shikimic acid and niraparib have a good interaction in holding the
molecule in place (binding) of the active site, and docking
investigations have been carried out using Molegro Virtual Docker
(MVD).
Keywords Shikimic acid pathway; BRCA1; BRCA2; Breast Cancer;
Lipinski rule; DPPH method;