| Autor: |
Elfaki EM; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences-Qurayyat, Jouf University, Qurayyat, Saudi Arabia., Alhassan HH; Department of Clinical Laboratory Science, College of Applied medical Sciences, Jouf University, Sakaka, Saudi Arabia., Kamal M; Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia., Al-Enazi MM; Department of Medical Laboratory Sciences, College of Applied Medical Sciences in Al-Kharj, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia., Rub MA; Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia., Asiri AM; Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia.; Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia., Ali M; Chemistry Department, Faculty of Science, Aligarh Muslim University, Aligarh, India., Marwani HM; Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia., Alharethi SH; Department of Biological Science, College of Arts and Science, Najran University, Najran, Saudia Arabia., Alotaibi MM; Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia., Azum N; Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia. |
| Abstrakt: |
Tyrosine-protein kinase CSK otherwise known as C-terminal Src kinase (CSK), is involved in multiple pathways and processes, including regulating cell growth, differentiation, migration, and immune responses. Altered expression of CSK has been associated with various complexities, including cancer, CD45 deficiency, Osteopetrosis and lupus erythematosus. Important auxiliary roles of CSK in cancer progression make it a crucial target in developing novel anticancer therapy. Thus, CSK inhibitors are of concern as potent immuno-oncology agents. In this perspective, phytochemicals can be a significant source for unraveling novel CSK inhibitors. In this study, we carried out a systematic structure-based virtual screening of bioactive phytoconstituents against CSK to identify its potential inhibitors. After a multi-step screening process, two hits (Shinpterocarpin and Justicidin B) were selected based on their druglike properties and binding affinity towards CSK. The selected hits were further analyzed for their stability and interaction via all-atom molecular dynamics (MD) simulations. The selected hits indicated their potential as selective binding partners of CSK, which can further be used for therapeutic development against CSK-associated malignancies.Communicated by Ramaswamy H. Sarma. |
