Abstract
Quercetin is a flavonoid presenting cytotoxicity against different cancer cell lines. We hypothesized that its core could serve as a scaffold for generating more potent compounds. A quercetin–alanine bioconjugate was synthesized, its cellular internalization was monitored through confocal microscopy and its cytotoxic activity was explored against ten different cell lines. The bioconjugate consistently illustrated enhanced cytotoxic activity with respect to the parent compound. A threefold enhancement in its cytotoxicity was revealed for HeLa, A549, MCF-7 and LNCaP cells. In silico studies suggested that quercetin–alanine possesses enhanced binding affinity to human estrogen receptor alpha corroborating to its activity to MCF-7, overexpressing this receptor. Spectrofluorimetric, calorimetric and in silico studies revealed that quercetin–alanine binds primarily to Sudlow site I of serum albumin mainly through hydrogen bonding. Through this array of experiments we discovered that the specific compound bears a more refined pharmaceutical profile in contrast to quercetin in terms of cytotoxicity, while at the same time preserves its affinity to serum albumin. Natural products could thus offer a potent scaffold to develop bioconjugates with amplified therapeutic window.
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This research project was supported by Greek national funds through the operational program “THESSALY-MAINLAND GREECE AND EPIRUS-2007 to 2013” of the National Strategic Reference Framework (NSRF 2007 to 2013).
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Chatziathanasiadou, M.V., Geromichalou, E.G., Sayyad, N. et al. Amplifying and broadening the cytotoxic profile of quercetin in cancer cell lines through bioconjugation. Amino Acids 50, 279–291 (2018). https://doi.org/10.1007/s00726-017-2514-2
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DOI: https://doi.org/10.1007/s00726-017-2514-2