Computational Screening of Natural Compounds for the Discovery of Potential Aromatase Inhibitors: A Promising Therapy for Estrogen-Dependent Breast Cancer
Misbahuddin M. Rafeeq
Department of Pharmacology. Faculty of Medicine, Rabigh. King Abdulaziz University. Jeddah, 21589, KSA.
Ziaullah M. Sain
Department of Microbiology Faculty of Medicine, Rabigh. King Abdulaziz University, Jeddah. 21589. KSA.
Norah A. Alturki
College of Applied Medical Science, Clinical Laboratory Science Department, King Saud University, Riyadh, Saudi Arabia.
Ahmad Alzamami
College of Applied Medical Science, Clinical Laboratory Science Department, Shaqra University, Saudi Arabia.
Saeed A. Asiri
Department of Clinical Laboratory Sciences, College of Applied Medical sciences, Najran University, Saudi Arabia.
Mutaib M. Mashraqi
Department of Clinical Laboratory Sciences, College of Applied Medical sciences, Najran University, Saudi Arabia.
Amany I. Alqosaibi
Department of Biology, College of Science, Imam Abdulrahman bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.
Mashael M. Alnamshan
Department of Biology, College of Science, Imam Abdulrahman bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.
Abdulrahman Almutairi
Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia.
Abdulkhaliq Munawir Alanazi
Department of Respiratory Services, Ministry of National Guard Hospital and Health Affairs (MNGHA), P.O.Box 22490, Kingdom of Saudi Arabia.
Qamre Alam *
Medical Genomics Research Department, King Abdullah International Medical Research Center King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City Riyadh 11426, Saudi Arabia.
*Author to whom correspondence should be addressed.
Abstract
Aromatase plays a significant role in the progression of estrogen receptor-positive (ER-positive) breast cancer. The adverse side effects of currently used aromatase inhibitors (AIs) necessitate the development of new AIs that are more active, selective, and less toxic. This study used a computational approach to screen 503 natural compounds ZINC database against the aromatase active site. The best scoring hits ZINC69482055, ZINC69482510, and ZINC406719 exhibited strong binding with aromatase, with binding energy values of -8.45, -10.35, and -8.75 kcal/mol, respectively, which is comparatively higher than that of the control compound Anastrozole (-6.43 kcal/mol). Docking analysis showed that the selected hits interacted with the crucial residues of the aromatase active site. This study suggested that these compounds could be used as possible AIs in the cure of breast cancer. Hands-on bench work validation is needed to optimize these compounds as AIs.
Keywords: Aromatase, breast cancer, natural compounds, estrogen receptor