Vibrational, theoretical characterisation and In Silico investigation of Norcinnamolaurine: a natural lead for inhibiting AURKA and overcoming immune evasion in Triple-Negative Breast Cancer

Alkaloids represent a diverse category of natural compounds with noteworthy pharmacological and therapeutic applications. Benzylisoquinoline alkaloids (BIAs) are distinguished by their varied structures and potential medicinal properties. This study specifically investigates Norcinnamolaurine, a BIA found in multiple species and acknowledged for its therapeutic advantages. In the current investigation, we comprehensively analyzed Norcinnamolaurine, encompassing Frontier Molecular Orbital studies, vibrational spectroscopy, nonlinear optical properties, natural bond orbital evaluations, and Fukui's analysis. Additionally, we executed an E-pharmacophore-based screening utilizing the AURKA-Norcinnamolaurine complex. The generated hypothesis underwent database screening; lead compounds from the Natural Product and Drug Bank databases exhibited enhanced binding affinities ranging from −8.602 to −7.148 kcal/mol, demonstrating improved interactions within the AURKA binding pocket. Subsequently, the identified lead compounds were subjected to further analysis via MMGBSA, DFT, and Molecular Dynamics Simulations (MDS). Our findings indicate that Norcinnamolaurine exhibits a superior binding affinity towards the target protein. Significant outcomes were also observed in the vibrational and FMO studies. Moreover, MDS analysis revealed that the resultant complexes maintained relative stability, exhibiting minimal deviation and fluctuations. This stability was corroborated through additional assessments using MMPBSA and PCA/FEL methodologies.