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Updated: Feb 28, 2026
Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Design, Synthesis, Biological Evaluation and Molecular Docking Studies of New N-Heterocyclic Compounds as Aromatase
Fatih Tok1, Begüm Nurpelin Sağlık Özkan2,3, Yusuf Özkay2,3
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, 34854 İstanbul, Türkiye.
Abstract:
Background/Objectives: Breast cancer is the most common cancer and the second leading cause of cancer death in women. The aromatase enzyme plays a role in estrogen biosynthesis and is an important biological target for breast cancer treatment. For this purpose, some new 1,3,4-thiadiazole (4a-4j) and 1,2,4-triazole (5a-5j) structures were designed and synthesized based on the structures of the existing aromatase inhibitors letrozole and anastrozole. Methods: The antiproliferative activities of the compounds were tested against MCF-7 cancer cells. The NIH3T3 healthy cells were used to evaluate the selectivity of the compounds. The inhibitory activities of all compounds were tested against the aromatase enzyme. Results: The 1,2,4-triazole derivatives 5b, 5c, 5e, 5f and 5g exhibited the highest antiproliferative activity against MCF7 cells with IC50 values ranging from 3.142 to 10.415 μM. Similar to the antiproliferative activity results, triazole derivatives 5b, 5c, 5e, 5f and 5g exhibited comparable anti-aromatase activity to letrozole (IC50 = 0.031 μM) with IC50 values ranging from 0.064 to 2.224 μM and demonstrated the highest anti-aromatase activity within the series. The interactions of compound 5c, the most potent compound based on activity results, with the aromatase enzyme have been elucidated through molecular docking and MD simulation studies. Conclusions: According to experimental studies and molecular docking findings, compound 5c shows promise for further studies with its aromatase enzyme inhibitory potential.
Insights
New 1,2,4-triazole derivatives show potent anti-aromatase activity and antiproliferative effects against breast cancer cells. Compound 5c demonstrates significant potential as an aromatase inhibitor for further research.
Area of Science:
- Medicinal Chemistry
- Oncology
- Biochemistry
Background:
- Breast cancer is a leading cause of cancer death in women.
- The aromatase enzyme is a key target for breast cancer treatment.
- Existing aromatase inhibitors include letrozole and anastrozole.
Purpose of the Study:
- To design and synthesize novel 1,3,4-thiadiazole and 1,2,4-triazole derivatives.
- To evaluate the antiproliferative and anti-aromatase activities of these compounds.
- To investigate the molecular interactions of potent compounds with the aromatase enzyme.
Main Methods:
- Synthesis of 1,3,4-thiadiazole (4a-4j) and 1,2,4-triazole (5a-5j) derivatives.
- Antiproliferative assays using MCF-7 breast cancer cells.
- Selectivity assessment using NIH3T3 healthy cells.
- Aromatase enzyme inhibition assays.
- Molecular docking and molecular dynamics (MD) simulations.
Main Results:
- 1,2,4-triazole derivatives 5b, 5c, 5e, 5f, and 5g showed significant antiproliferative activity against MCF-7 cells (IC50: 3.142–10.415 μM).
- These triazole derivatives also exhibited potent anti-aromatase activity, comparable to letrozole (IC50: 0.064–2.224 μM).
- Compound 5c was identified as the most potent, with its interactions with aromatase elucidated via molecular docking and MD simulations.
Conclusions:
- Compound 5c demonstrates significant aromatase enzyme inhibitory potential.
- The synthesized 1,2,4-triazole derivatives hold promise for breast cancer treatment.
- Further studies on compound 5c are warranted based on its efficacy and molecular interactions.
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