Synthesis of novel isoflaveneapropranolol hybrids as anti-tumor agents

Isoflaveneapropranolol hybrid molecules were developed as potentially novel anti-tumour agents. Isoflavene itself has potent anti-cancer activity while propranolol can enhance anti-proliferative and anti-angiogenic properties of 5-fluorouracil and paclitaxel. The hybrids were produced via nucleophil...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2013-04, Vol.21 (7), p.1652-1660
Main Authors: Yee, Eugene MH, Pasquier, Eddy, Iskander, George, Wood, Kasey, Black, David StC, Kumar, Naresh
Format: Article
Language:English
Subjects:
5-Fluorouracil
Adenocarcinoma
amines
Endothelial cells
Fibroblasts
Microvasculature
Paclitaxel
Propranolol
Tumor cell lines
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Summary:Isoflaveneapropranolol hybrid molecules were developed as potentially novel anti-tumour agents. Isoflavene itself has potent anti-cancer activity while propranolol can enhance anti-proliferative and anti-angiogenic properties of 5-fluorouracil and paclitaxel. The hybrids were produced via nucleophilic addition of substituted amine groups to a dioxiran intermediate, which was in turn generated from the Williamson-type reaction of isoflavene with (+/-)-epichlorohydrin. These analogues were tested in anti-cancer cell viability assays against SHEP neuroblastoma and MDA-MB-231 breast adenocarcinoma cell lines, and were found to exhibit potent anti-proliferative activities. These compounds also displayed anti-angiogenic and anti-proliferative effects in HMEC-1 human microvascular endothelial cell lines. Notably, the most potent hybrid molecules synthesized in this work showed enhanced potency against cancer cell lines compared to either isoflavene or propranolol alone, while retaining significant selectivity for cancer cells over MRC-5 normal lung fibroblast cells.
ISSN:0968-0896
DOI:10.1016/j.bmc.2013.01.059