Semi-Synthesis of New 1,2,3-Triazole Derivatives of 9-Bromonoscapine and their Anticancer Activities

Document Type: Research article

Authors

1 Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran.

2 Schulich School of Medicine and Dentistry and Robarts Research Institute, Western University, London, Ontario, Canada.

3 Institute of Pharmacy, Pharmacognosy, Center for Molecular Biosciences, University of Innsbruck, 6020 Innsbruck, Austria.

Abstract

Novel 1,2,3-triazole-tethered 9-bromonoscapine derivatives were synthesized by the propargylation of N-nornoscapine followed by Huisgen’s 1,3-dipolar cycloaddition of the terminal alkynes with different azides. Cytotoxicity of the products was studied by MTT assay against the MCF-7 breast cancer cell line. Most of the compounds revealed a better cytotoxicity than N-nornoscapine and 9-bromonornoscapine as the parent compounds. Among the synthesized compounds, those with a hydroxylated aliphatic side chain (5p, 5q, and 5r) showed the highest activities (IC50s: 47.2, 37.9, and 32.3 μg/mL, respectively). Molecular docking studies showed that these compounds also had the highest docking scores and effective interactions with binding sites equal to -8.074, -7.425 and -7.820 kcal/mol, respectively.

Graphical Abstract

Semi-Synthesis of New 1,2,3-Triazole Derivatives of 9-Bromonoscapine and their Anticancer Activities

Keywords