Multitargeted docking approach reveals droxidopa against DNA replication and repair-related protein of cervical cancer.

Autor: Alsaiari AA; Department of Clinical Laboratory Science, College of Applied Medical Science, Taif University, Taif, 21944, Saudi Arabia., Almufarriji FM; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Al-Quwayiyah, 19257, Saudi Arabia., Hazazi A; Department of Pathology and Laboratory Medicine, Security Forces Hospital Program, Riyadh, Saudi Arabia.; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia., Almarghalani DA; Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia.; Stroke Research Unit, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia., Bakhuraysah MM; Department of Clinical Laboratory Science, College of Applied Medical Science, Taif University, Taif, 21944, Saudi Arabia., Alrehaili AA; Department of Clinical Laboratory Science, College of Applied Medical Science, Taif University, Taif, 21944, Saudi Arabia., Algethami SM; Department of Clinical Laboratory Science, College of Applied Medical Science, Taif University, Taif, 21944, Saudi Arabia., Almehmadi KA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia., Bahwerth FS; Molecular Genetics Department, King Faisal Hospital, Riyadh, Saudi Arabia., Hakami MA; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Al-Quwayiyah, 19257, Saudi Arabia. m.hakami@su.edu.sa.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Oct 16; Vol. 14 (1), pp. 24301. Date of Electronic Publication: 2024 Oct 16.
DOI: 10.1038/s41598-024-72770-9
Abstrakt: Cervical cancer begins in the cells lining the cervix and is caused by persistent infection with certain types of human papillomavirus (HPV). Initially, it has no symptoms, and later it causes pelvic pain, abnormal vaginal bleeding, and pain during intercourse. It is the fourth-ranked cancer among women, and many women die from cervical cancer every year, particularly in low-income countries and the majority could be prevented with early detection and treatment. In this study, we have taken Cervical Cancer DNA Replication and Repair-Related Protein with the PDBID- 3H15, 5VBN, and 6NT9 and performed the multitargeted molecular docking with the FDA-approved drug library using HTVS, SP and XP docking. Then, the poses were filtered with MM\GBSA for proper computations of free energy, identified a multitargeted inhibitor Droxidopa with docking and MM\GBSA scores ranging from - 5.559 to - 6.835 Kcal/mol and - 26.04 to - 37.33 Kcal/mol, respectively. We also performed interaction fingerprints revealing 2VAL, 2LYS, 1ALA, 1ARG, 1ASN, 1CYS, 1GLN, 1GLU, 1ILE, 1MET, 1PHE, 1PRO, 1SER, and 1THR were most interacted residues and computed the ADMET properties with QikProp and DFT with Jaguar, which supported the study and compounds' suitability. Moreover, we performed the 100ns MD simulation in water, showing the controlled deviation and fluctuations of the residues with many interactions, and MM\GBSA was performed with the same trajectories, showing a better understanding of each frame's total complex and binding-free energy. The whole study favours droxidopa as an inhibitor of cervical cancer DNA Replication and Repair-Related Proteins-however, experimental studies are needed before use.
(© 2024. The Author(s).)
Databáze: MEDLINE
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