In silico identification of novel natural compounds as potential KIFC1 inhibitors for the therapeutic intervention of triple-negative breast cancer.

TNBC is an aggressive and various subtype of breast cancer, notable by the lack of specific oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), consequential in limited treatment options and poor prognosis. Kinesin Family Member C1 (KIFC1), a mitotic motor protein critical for centrosome clustering and spindle formation, has critical role in TNBC progress. In this situation, natural compounds were explored as probable inhibitors of this protein. we utilized molecular docking, ADMET profiling, density functional theory calculations, molecular dynamics simulations, MM/GBSA binding free energy analysis, and principal component analysis to thoroughly evaluate binding affinity, stability, and drug-likeness property of natural compounds against KIFC1. Of the 36,900 compounds utilized, five natural compounds were carefully chosen for further assessment. All five compounds Fosfocytocin, Molybdopterin Compound Z, 5-amino-2-(3-hydroxy-13-methyltetradecanamido) pentanoic acid, TMC-52A, and Muscimol exhibited significant inhibitory efficacy against KIFC1. These compounds demonstrated persistent interactions with critical residues and had advantageous binding properties in computational evaluations. The results collectively indicate their potential as effective inhibitors for targeting KIFC1 in forthcoming studies. These data collectively identify all five natural compounds as possible inhibitors of KIFC1. Nonetheless, their effectiveness and safety must be confirmed through in vivo and in vitro study prior to consideration for clinical application.