Title
Molecular docking analysis of MCL-1 inhibitors for breast cancer management
Authors
Abdulrahman Alzahrani1, Mohammad Azhar Kamal2, Asif Hussain Akber3, Ali Abdullah Asiri4, Marui Ibrahim Shafei5, Mohammed Hadi Ghawi6, Hanan Mamdouh Alotaibi7, Qamre Alam8,*
Affiliation
1Department of Applied Medical Sciences, Applied College, Al-Baha University, Al-baha City, Kingdom of Saudi Arabia; 2Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia; 3Central Military Laboratory and Blood Bank Department – Virology Division, Prince Sultan Military Medical City, Riyadh 12233, Saudi Arabia; 4Central Military Laboratory and Blood Bank Department - Microbiology Lab Division, Prince Sultan Military Medical City, Riyadh 12233, Saudi Arabia; 5Central Military Laboratory and Blood Bank Department - Hematology Lab Division, Prince Sultan Military Medical City, Riyadh 12233, Saudi Arabia; 6Central Military Laboratory and Blood Bank Department - Hematology Lab Division, Prince Sultan Military Medical City, Riyadh 12233, Saudi Arabia; 7Central Military Laboratory and Blood Bank Department - Microbiology Lab Division, Prince Sultan Military Medical City, Riyadh 12233, Saudi Arabia; 8Molecular Genomics and Precision Medicine Department, ExpressMed Diagnostics and Research, Block, 359, Zinj, Kingdom of Bahrain; *Corresponding Author
Abdulrahman Alzahrani - E-mail: abdulrahmanmuidh@gmail.com
Mohammad Azhar Kamal - E-mail: ma.kamal@psau.edu.sa
Asif Hussain Akber - E-mail: asif20000@gmail.com
Ali Abdullah Asiri - E-mail: ali.alfalgy78@gmail.com
Marui Ibrahim Shafei - E-mail: mshafei@psmmc.med.sa
Mohammed Hadi Ghawi - E-mail: mghawi@psmmc.med.sa
Hanan Mamdouh Alotaibi - E-mail: hmnalotaibi@psmmc.med.sa
*Qamre Alam - E-mail: alamqa2022@gmail.com
Article Type
Research Article
Date
Received June 1, 2023; Revised June 30, 2023; Accepted June 30, 2023, Published June 30, 2023
Abstract
Myeloid leukemia 1 (MCL-1), a BCL-2 protein family member, acts as an anti-apoptotic protein by interacting with pro-apoptotic BCL-2 proteins. Its overexpression is frequently observed in numerous cancer types including breast cancer, and is closely linked to the initiation and progression of tumors as well as poor prognosis and resistance to therapeutic interventions. Here, a database of 3402 chemicals with established therapeutic activity against various diseases was chosen and systematically screened against the MCL-1 protein. Visual inspection and binding energy analysis revealed that the compounds OSU-03012, Raltitrexed, Ostarine (MK-2866), Dovitinib (TKI-258), and Varespladib (LY315920) had strong binding affinity for the MCL-1 protein. Notably, their binding affinity was higher than that of the control compounds. These compounds exhibited strong interactions with critical amino acid residues of the MCL-1 protein. Furthermore, these compounds shared several common amino acid residue interactions with the control compounds. These findings suggest that these compounds may be useful as MCL-1 inhibitors in the treatment of breast cancer. However, additional experimental validation is required to confirm these findings.
Keywords
Myeloid leukemia 1, breast cancer, virtual screening, apoptosis.
Citation
Alzahrani et al. Bioinformation 19(6): 707-712 (2023)
Edited by
P Kangueane
ISSN
0973-2063
Publisher
License
This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.
