QSAR-based virtual screening of traditional Chinese medicine for the identification of mitotic kinesin Eg5 inhibitors

Cell division is a crucial process for the growth and development of all living organisms. Unfortunately, uncontrolled cell division and growth is a hallmark of cancer, leading to the formation of tumors. The Human Eg5 protein, also known as the mitotic kinesin Eg5, plays a vital role in the regulation of cell division and its dysfunction has been linked to cancer development. This study aimed to identify new inhibitors of the Human Eg5 protein. Over 2000 Traditional Chinese Medicine (TCM) compounds were screened through a combination of virtual and structure-based screening methods. The top five compounds (Compounds 1–5) showed improved binding affinity to Human Eg5 compared to the standard drug Monastrol, as demonstrated by docking and MMGBSA scores, as well as interactions with key amino acids GLY 116 and GLY 118. The potential absorption and bioactivity of these compounds were also predicted through ADMET properties and a QSAR model, respectively, and showed improved results compared to the standard. Further quantum mechanics docking confirmed the better binding affinity of the lead compound, Compound 1. Our findings highlight Compound 1–5 as promising hits for inhibiting Human Eg5 and the need for experimental validation of their potential in treating cancer. [Display omitted] •Pharmacophore modeling, QSAR, and virtual screening identified potential Eg5 inhibitors from a TCM library.•Top-ranked compounds had better potential than Monastrol as Eg5 inhibitors based on pIC50, docking, MMGBSA, and ADME parameters.•Compound 1 was identified as the lead compound with stronger binding affinity to Eg5 than Monastrol using QPLD.•Molecular dynamics simulation supported QPLD, indicating Compound 1 has more stable binding and longer duration of action potential.