Abstract
Direct nitration of estradiol was carried out using metal nitrates on solid surfaces under mild condition, and a combination of bismuth nitrate pentahydrate impregnated KSF clay was found to be the best reagent to synthesize 2- and 4-nitroestradiol effectively. Furthermore, various basic side chains were introduced, through O-linker at C-3, to these nitroestradiols. The ability of these derivatives to cause cytotoxicity in Estrogen Receptor (ER)-positive and ER-negative breast cancer cell lines, as well as cancer cell lines of other origins, was examined. Qualitative structure activity relationship (SAR) has also been studied. We found that a basic side chain containing either a piperidine or morpholine ring, when conjugated to 2-nitroestradiol, was particularly effective at causing cytotoxicity in each of the cancer cell lines examined. Surprisingly, this effective cytotoxicity was even seen in ER-negative breast cancer cells.
Original language | English |
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Pages (from-to) | 574-583 |
Number of pages | 10 |
Journal | European Journal of Medicinal Chemistry |
Volume | 82 |
DOIs | |
State | Published - 23 Jul 2014 |
Keywords
- Anticancer
- Apoptosis
- Bismuth nitrate
- Estradiol
- Estrogen receptor
- Nitration
- Solid-support