Identification of <i>N</i> ‐(2‐(1H‐indol‐3‐yl) ethyl)‐ <i>N</i> ‐benzylacrylamide as Novel Aurora Kinase A Inhibitor for Cancer Therapy: Virtual Screening, Synthesis, MD Simulation, and In Vitro Validation

ABSTRACT Aurora kinase A (AURKA) is a key regulator of mitotic entry, playing a critical role in centrosome separation and overall mitotic progression. Due to its fundamental involvement in cell division and its implication in tumorigenesis, AURKA has emerged as a compelling target for anticancer therapy. Despite ongoing efforts, no highly specific and effective drug has yet been approved against this enzyme. Consequently, the development of aurora kinase inhibitors (AKIs) remains a vibrant field of research, driven by their potential to exert strong antiproliferative effects and inhibit tumor growth. The objective of this study was to discover novel inhibitors of AURKA with potential therapeutic application in cancer treatment. In this study, ligands sourced from the ZINC15 database were subjected to descriptor‐based and docking‐based virtual screening. The Top 10 compounds identified through docking were further evaluated for their ADME properties and toxicity profiles. Based on synthetic accessibility, a selected hit compound was synthesized and subsequently analyzed through molecular dynamics (MD) simulation. The synthesized compound was then assessed using cell viability and enzyme inhibition assays. Compound N ‐benzyl‐2‐(1H‐indol‐3‐yl) ethanamine (ZINC00338365) was identified as exhibiting strong binding interactions with AURKA, along with favorable drug‐likeness, efficient ADME properties, lack of toxicity, and high stability. Furthermore, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) and enzyme inhibition assays demonstrated its potent antiproliferative activity. This study demonstrates, for the first time, that the compound ZINC00338365 binds to AURKA, effectively inhibits its function, and induces cytotoxicity through apoptosis. The findings indicate that the compound exhibits a safe profile and is druggable, highlighting its potential as a promising candidate for cancer therapy.