Affiliation:
1. Department of Biology, Turabah College, Taif University, Taif-21944, Kingdom of Saudi Arabia
2. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran-61441, Kingdom of Saudi Arabia
3. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif-21944, Kingdom of Saudi Arabia
Abstract
Background:
Cervical cancer originates in the cervix, the lower part of the
uterus, and results from the uncontrolled growth of abnormal cervical cells, forming malignant
tumours. It poses a major global health challenge, calling for innovative drug design
strategies to enhance treatment outcomes.
Method:
In this study, we have screened the FDA-approved drug library against four
proteins, MCM10, MCM6, DNA polymerase epsilon subunit-2, and TBK1, which are essential
for DNA replication, DNA repair, and cellular signalling pathways, which are
dysregulated in cervical cancer cells, leading to uncontrolled growth. We have used the
multisampling algorithms for screening using HTVS, SP, and XP docking; identified 6-
oxidopamine HBr (C8H12BrNO3), which is used to create a model of Parkinson’s disease
in animals, and obtained the docking score ranging from -5.057 to -8.871 Kcal/mol. The
poses were filtered with MM\GBSA score ranging from -21.67 to -27.63 Kcal/mol. We
performed QM-based DFT and pharmacokinetics studies and compared them with the
standard values, suggesting that the compound can be used in cervical cancer proteins.
Result:
The P-L complex’s interaction fingerprints have resulted in the most interacting
residues, 4THR, 4SER, and 4LYS, showing the compound’s interaction pattern.
Conclusion:
Further, the stability of 6-oxidopamine HBr in complex with each protein
was evaluated with 100ns MD simulation in the SPC water model in a neutralised state
to analyse the deviation, fluctuations, and intermolecular interactions that have proven
the compound to have a better inhibitory effect against each protein and that it can be
used for cervical cancer; however, experimental validation is suggested before human
use.
Publisher
Bentham Science Publishers Ltd.
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献