Affiliation:
1. Department of Pharmaceutical Sciences College of Pharmacy and Health Sciences St. John's University 8000 Utopia Parkway Queens, NY 11439 (S.Y.)
2. Current affiliation: The Scripps Research Institute 10550 N Torrey Pines Rd. La Jolla CA 92037
3. Current affiliation: Department of Biochemistry and Molecular Biotechnology University of Massachusetts Medical School Worcester MA 01605
Abstract
AbstractSiderophores are structurally unique medicinal natural products and exhibit considerable therapeutic potential. Herein, we report the design and synthesis of azotochelin, a natural siderophore, and an extensive library of azotochelin analogs and their anticancer properties. We modified the carboxylic acid and the aromatic ring of azotochelin using various chemical motifs. We evaluated the cytotoxicity of the compounds against six different cancer cell lines (KB‐3‐1, SNB‐19, MCF‐7, K‐562, SW‐620, and NCI−H460) and a non‐cancerous cell line (HEK‐293). Among the twenty compounds tested, the IC50 values of nine compounds (14, 32, 35–40, and 54) were between 0.7 and 2.0 μM against a lung cancer cell line (NCI−H460). Moreover, several compounds showed good cytotoxicity profile (IC50 <10 μM) against the tested cancer cell lines. The flow cytometry analysis showed that compounds 36 and 38 induced apoptosis in NCI−H460 in a dose‐dependent manner. The cell cycle analysis indicated that compounds 36 and 38 significantly arrested the cell cycle at the S phase to block cancer cell proliferation in the NCI−H460 cell line. The study has produced various novel azotochelin analogs that are potentially effective anticancer agents and lead compounds for further synthetic and medicinal chemistry exploration.