Τίτλος:
Amplifying and broadening the cytotoxic profile of quercetin in cancer cell lines through bioconjugation
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2017, Springer-Verlag GmbH Austria, part of Springer Nature.
Συγγραφείς:
Chatziathanasiadou, M.V.
Geromichalou, E.G.
Sayyad, N.
Vrettos, E.I.
Katsikoudi, A.
Stylos, E.
Bellou, S.
Geromichalos, G.D.
Tzakos, A.G.
Περιοδικό:
Journal of Amino Acids
Εκδότης:
Springer-Verlag Wien
Λέξεις-κλειδιά:
antineoplastic agent; bovine serum albumin; estrogen receptor alpha; quercetin; quercetin alanine bioconjugate; unclassified drug; alanine; antineoplastic agent; biological product; flavonoid; protein binding; quercetin; serum albumin, A-549 cell line; animal cell; antineoplastic activity; Article; binding affinity; cancer inhibition; computer model; conjugation; controlled study; drug binding site; drug cytotoxicity; drug potency; drug protein binding; drug receptor binding; drug sensitivity; drug structure; HeLa cell line; human; human cell; hydrogen bond; IC50; internalization; LNCaP cell line; MCF-7 cell line; molecular docking; mouse; nonhuman; priority journal; umbilical vein endothelial cell; analogs and derivatives; animal; cell proliferation; cell survival; chemistry; comparative study; dose response; drug effect; drug screening; metabolism; structure activity relation; synthesis; tumor cell line, Alanine; Animals; Antineoplastic Agents; Biological Products; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Flavonoids; Humans; Inhibitory Concentration 50; Mice; Molecular Docking Simulation; Protein Binding; Quercetin; Serum Albumin; Structure-Activity Relationship
DOI:
10.1007/s00726-017-2514-2
