1. Synthesis, biological evaluation and structure-activity relationship studies of isoflavene based Mannich bases with potent anti-cancer activity.
- Author
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Chen Y, Cass SL, Kutty SK, Yee EM, Chan DS, Gardner CR, Vittorio O, Pasquier E, Black DS, and Kumar N
- Subjects
- Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Antineoplastic Agents toxicity, Breast Neoplasms drug therapy, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Drug Screening Assays, Antitumor, Female, Fibroblasts cytology, Fibroblasts drug effects, Humans, Inhibitory Concentration 50, Mannich Bases chemistry, Mannich Bases toxicity, Molecular Structure, Structure-Activity Relationship, Isoflavones chemical synthesis, Isoflavones chemistry, Isoflavones toxicity, Mannich Bases chemical synthesis, Mannich Bases pharmacology
- Abstract
Phenoxodiol, an analogue of the isoflavone natural product daidzein, is a potent anti-cancer agent that has been investigated for the treatment of hormone dependent cancers. This molecular scaffold was reacted with different primary amines and secondary amines under different Mannich conditions to yield either benzoxazine or aminomethyl substituted analogues. These processes enabled the generation of a diverse range of analogues that were required for structure-activity relationship (SAR) studies. The resulting Mannich bases exhibited prominent anti-proliferative effects against SHEP neuroblastoma and MDA-MB-231 breast adenocarcinoma cell lines. Further cytotoxicity studies against MRC-5 normal lung fibroblast cells showed that the isoflavene analogues were selective towards cancer cells., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2015
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