“Design, Synthesis and Biological Evaluation of Some Heterocycles as Non-Steroidal Aromatase Inhibitors”
Keywords:
Breast cancer, Flavonoids, Aromatase inhibitors, Molecular docking, Synthesis, Antioxidant activity, Cytotoxicity, MCF-7 cell line.
Abstract
Cancer remains a critical global health issue and is the second leading cause of death after cardiovascular diseases, accounting for 1 in 6 deaths globally. By 2050, cancer cases are projected to rise to 27 million, with 17.5 million deaths due to demographic shifts. Breast cancer stands out as the most common cancer among women, with a significant incidence rate reported across various regions, including India, where it constitutes 25-32% of all female cancers. Efforts to combat breast cancer have focused on the study of flavonoids, both natural and synthetic, which are known to inhibit the aromatase enzyme. This study involved designing 76 flavonoid derivatives, whose novelty was verified through databases like Sci-Finder and PubChem. Using Molecular Docking with Glide software, 40 compounds were selected for synthesis based on their docking scores. The synthesis involved chalcone derivatives, followed by ring cyclization, resulting in a 49-94% yield of flavonoid derivatives.
The synthesized compounds were characterized by spectroscopic techniques and tested for their antioxidant and cytotoxic properties. Out of 30 compounds tested for antioxidant activity, 18 were further examined for their effectiveness against breast cancer cell lines (MCF-7) through MTT assays. Compounds 6B, 2K, 4K, 6K, 4B, 2B, and 4C demonstrated superior cytotoxicity compared to the standard drug Letrozole. Six of these compounds were also assessed for aromatase inhibitory activity, with compounds 2B and 6B showing potent inhibition, outperforming Letrozole. These findings suggest that specific flavonoid derivatives hold promise as effective treatments against breast cancer, potentially surpassing current standards.
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36. Hoshino J., Park E.-J., Kondratyuk T.P., Marler L., Pezzuto J.M., van Breemen R.B., Mo S., Li Y., Cushman M. Selective Synthesis and Biological Evaluation of Sulfate-Conjugated Resveratrol Metabolites. J. Med. Chem. 2010;53:5033–5043. doi: 10.1021/jm100274c. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
Published
2024-06-25
How to Cite
Saajan Kumar, Dr. Arun Patel, & Mr. Shailendra Patel. (2024). “Design, Synthesis and Biological Evaluation of Some Heterocycles as Non-Steroidal Aromatase Inhibitors”. Revista Electronica De Veterinaria, 25(1), 852-869. https://doi.org/10.69980/redvet.v25i1.731
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