Abstract
Background: In an effort to establish new drug candidates with improved antiproliferative activity, we report here a novel class of compounds designed rationally by the replacement of an ethyl group in tamoxifen with a methylene (1H-1,2,4-triazole) and the introduction of 1,4- substituted 1,2,3-triazoles in the basic side chain.
Methods: Magnetically separable iron oxide nanoparticles have been found to effectively catalyze the one-pot multicomponent click synthesis of 1,4-disubstituted 1,2,3-triazole conjugates in water. IR, 1HNMR, 13CNMR and HRMS experiments have been implemented for the unmistakable determination of the regiochemistry of the process. The novel compounds were evaluated for their antiproliferative activity against four human tumor cell lines, namely, MCF-7, MDA-MB-231, HeLa, and A549. Cell growth inhibition was assessed according to the standard Sulforhodamine B (SRB) cell proliferation method.
Results: The most active compounds 4h, 4n and 5a have been identified with superior GI50 values in the range of 0.13–0.31 µM as compared with the reference drug, tamoxifen (0.25-0.72 µM).
Conclusion: Additionally, taking the stereochemistry into consideration, E isomers seem slightly more active towards the tested cancer cell lines with respect to Z isomers.
Keywords: Tamoxifen, triazole, click chemistry, nano iron oxide, antiproliferative activity, stereochemistry.
Graphical Abstract
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