title: Binding mode of triazole derivatives as aromatase inhibitors based on docking, protein ligand interaction fingerprinting, and molecular dynamics simulation studies.
abstract: Aromatase inhibitors (AIs) as effective candidates have been used in the treatment of hormone-dependent breast cancer. In this study, we have proposed 300 structures as potential AIs and filtered them by Lipinski's rule of five using DrugLito software. Subsequently, they were subjected to docking simulation studies to select the top 20 compounds based on their Gibbs free energy changes and also to perform more studies on the protein-ligand interaction fingerprint by AuposSOM software. In this stage, anastrozole and letrozole were used as positive control to compare their interaction fingerprint patterns with our proposed structures. Finally, based on the binding energy values, one active structure (ligand 15) was selected for molecular dynamic simulation in order to get information for the binding mode of these ligands within the enzyme cavity. The triazole of ligand 15 pointed to HEM group in aromatase active site and coordinated to Fe of HEM through its N4 atom. In addition, two π-cation interactions was also observed, one interaction between triazole and porphyrin of HEM group, and the other was 4-chloro phenyl moiety of this ligand with Arg115 residue.
authors.affiliation: Department of Medicinal Chemistry and Pharmaceutical Sciences Research Centre, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, I.R. Iran.
authors.forename: Ayyub
authors.initials: A
authors.lastname: Mojaddami
authors.affiliation: Department of Medicinal Chemistry and Pharmaceutical Sciences Research Centre, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, I.R. Iran.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sakhteman
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, I.R. Iran.
authors.forename: Masood
authors.initials: M
authors.lastname: Fereidoonnezhad
authors.affiliation: Department of Medicinal Chemistry and Pharmaceutical Sciences Research Centre, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, I.R. Iran.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Faghih
authors.affiliation: Department of Nuclear Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, I.R. Iran.
authors.forename: Atena
authors.initials: A
authors.lastname: Najdian
authors.affiliation: Department of Medicinal Chemistry and Pharmaceutical Sciences Research Centre, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, I.R. Iran.
authors.forename: Soghra
authors.initials: S
authors.lastname: Khabnadideh
authors.affiliation: Department of Medicinal Chemistry and Pharmaceutical Sciences Research Centre, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, I.R. Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Sadeghpour
authors.affiliation: Department of Medicinal Chemistry and Pharmaceutical Sciences Research Centre, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, I.R. Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Rezaei
keywords: Aromatase inhibitor; Breast cancer; MD simulation; Molecular docking