Targeting chromosomal instability in patients with cancer

Al-Rawi, Duaa H.; Lettera, Emanuele; Li, Jun; DiBona, Melody; Bakhoum, Samuel F.

doi:10.1038/s41571-024-00923-w

Cited by 5 publications

(1 citation statement)

References 193 publications

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“…The Aurora proteins family of serine/threonine kinases plays key roles in the event of mitosis, chromosome segregation, and cytokines [1]. During mitosis, the change in the organization of DNA due to incorrect segregation of chromosomes and unbalanced control in cell cycle checkpoints are the major characteristics of most tumour cells.…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Quantitative Structure-Activity Relationships and Molecular Dynamic Simulations Studies to Discover Aurora Kinase-B Inhibitors

Anand,

Kabilan

2024

Preprint

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The serine-threonine kinase gene Aurora B kinase plays a critical role in spindle assembly, chromosome alignment, mitotic checkpoint activation, and cytokinesis. The overexpression of Aurora B causes errors in cell division and multinucleation in centrosome numbers leads to cancer. Three dimensional Quantitative Structure Activity Relationship studies were conducted on known inhibitors to find valid pharmacophore hypotheses. The five features hypothesis AADRR with better parameters using partial least square analysis has been selected for virtual screening. Molecular docking was applied to find the binding mode interactions of ligands with the Aurora-B binding pocket. Lys 106, Ala 157, Glu 161, and Phe 219 were identified as crucial residues that formed several interactions with the ligands which are essential for Aurora B inhibition. After the different levels of screening, five compounds from the National Cancer Institute database were acknowledged as novel inhibitors of Aurora B. The active site interactions of the protein-ligand complex were examined by molecular dynamics simulation studies.

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Section: Introductionmentioning

confidence: 99%