Synthesis of New 1,2,3-Triazole-Based Compounds of Potential Anti-Breast Cancer Activity Targeting Aromatase Enzyme Inhibition

Syam, Yasmin M.; EL-Hggar, Radwan; Anwar, Manal M.; Hisham, Alaa H.; Nosseir, Ola; Zaghary, Wafaa A.

doi:10.21608/ejchem.2023.179241.7278

Synthesis of New 1,2,3-Triazole-Based Compounds of Potential Anti-Breast Cancer Activity Targeting Aromatase Enzyme Inhibition

Document Type : Original Article

Authors

¹ Department of Therapeutic Chemistry, National Research Centre, Dokki, Cairo, Egypt

² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ain Helwan, 11795, Cairo, Egypt.

³ Therapeutic Chemistry Department, National Research Centre, Cairo, Egypt.

⁴ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ain Helwan, 11795, Cairo, Egypt

⁵ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, P.O. Box 11795, Cairo, Egypt

10.21608/ejchem.2023.179241.7278

Abstract

Depriving the estrogen in the body by inhibiting the aromatase enzyme is thought to be one of the most effective pathways for preventing and treating breast cancer. This study deals with the synthesis of new derivatives bearing a 4-bromophenyl-5-methyl-1,2,3-triazole scaffold hybridized with various heterocyclic rings of reported aromatase inhibition activity such as pyridine, pyrimidine, and pyrazole 4-14, aiming to gain new potent antiproliferative molecules against breast cancer via inhibition of the aromatase enzyme. The cytotoxic activity of the target compounds was evaluated against breast cancer (MCF-7) as well as the normal cell line (WI-38). The derivatives 5b, 5c and 10 were the most promising analogues with a high safety margin against WI38. The latter derivatives were also assessed as aromatase inhibitors and were also subjected to molecular docking studies to determine their potential.

Keywords