Academic Journal

Synthesis, Characterization, and In Vitro and In Silico Studies of New Triazole Derivatives as Aromatase Inhibitors.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Synthesis, Characterization, and In Vitro and In Silico Studies of New Triazole Derivatives as Aromatase Inhibitors.
Συγγραφείς: Uzmez ZL; Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey., Osmaniye D; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.; Central Analysis Laboratory, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey., Ozkay Y; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.; Central Analysis Laboratory, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey., Kaplancıklı ZA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.
Πηγή: Medicinal chemistry (Shariqah (United Arab Emirates)) [Med Chem] 2025; Vol. 21 (4), pp. 309-318.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Bentham Science Publishers Country of Publication: Netherlands NLM ID: 101240303 Publication Model: Print Cited Medium: Internet ISSN: 1875-6638 (Electronic) Linking ISSN: 15734064 NLM ISO Abbreviation: Med Chem Subsets: MEDLINE
Imprint Name(s): Publication: Amsterdam : Bentham Science Publishers
Original Publication: Sharjah, U.A.E.; San Francisco, CA : Bentham Science Publishers
Ιατρικοί όροι (MeSH): Aromatase Inhibitors*/pharmacology , Aromatase Inhibitors*/chemical synthesis , Aromatase Inhibitors*/chemistry , Triazoles*/pharmacology , Triazoles*/chemical synthesis , Triazoles*/chemistry , Antineoplastic Agents*/chemical synthesis , Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/chemistry, Aromatase/metabolism ; Cell Proliferation/drug effects ; Humans ; Structure-Activity Relationship ; Molecular Docking Simulation ; Drug Screening Assays, Antitumor ; MCF-7 Cells ; Molecular Structure ; A549 Cells ; Dose-Response Relationship, Drug
Περίληψη: Introduction: Breast cancer is the most common type of cancer among women. Steroidal or non-steroidal aromatase inhibitors (NSAIs) are used clinically, and in most cancer diseases, resistance is the most important problem.
Methods: The nitrogenous heterocyclic ring is noteworthy in the structure of non-steroidal aromatase inhibitors. This is the pharmacophore structure for aromatase inhibition. Because the enzyme interacts with the Fe2+ cation of the HEM structure in its active site, the most used agents in the clinic, such as anastrozole and letrozole, contain triazoles in their structures. Within the scope of this study, hybrid compounds containing both imidazole and triazole were synthesized.
Results: The synthesis was carried out by a 4-step reaction. The anticancer effects of the compounds were evaluated by MTT assay performed on A549 and MCF-7 cancer cells. Compound 4d showed anticancer activity against the MCF-7 cell line with IC50=6.7342 uM value. This compound exhibited anticancer activity against the A549 cell line with an IC50 = 17.1761 μM. In the MTT test performed on a healthy cell line to determine the cytotoxic effects of the compounds, the compound showed activity with a value of 4d IC50=13.2088 uM. This indicates that the compound is not cytotoxic. Additionally, BrdU analysis was performed to evaluate whether the compound inhibits DNA synthesis. These selective effects of the compounds on breast cancer strengthened their aromatase enzyme inhibitor potential. For this reason, experiments conducted with both in vitro and in silico methods revealed a compound with high aromatase inhibitor potential.
Conclusion: The interactions observed as a result of molecular docking and dynamics studies are in harmony with activity studies. In particular, interactions with HEM600 demonstrate the activity potential of the compound.
(Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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Grant Information: 1919B012201803 Research Fund of Tubitak 2209-A project
Contributed Indexing: Keywords: Breast cancer; aromatase inhibitor; estrogen.; molecular docking; molecular dynamics; triazole
Substance Nomenclature: 0 (Aromatase Inhibitors)
0 (Triazoles)
0 (Antineoplastic Agents)
EC 1.14.14.1 (Aromatase)
Entry Date(s): Date Created: 20250512 Date Completed: 20250512 Latest Revision: 20251114
Update Code: 20260130
PubMed Central ID: PMC12606616
DOI: 10.2174/0115734064316112240722092935
PMID: 40351069
Βάση Δεδομένων: MEDLINE