1. Biological macromolecule binding and anticancer activity of synthetic alkyne-containing L-phenylalanine derivatives.
- Author
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Fik-Jaskółka MA, Mkrtchyan AF, Saghyan AS, Palumbo R, Belter A, Hayriyan LA, Simonyan H, Roviello V, and Roviello GN
- Subjects
- Antineoplastic Agents chemistry, Binding Sites, Cell Proliferation, Humans, Molecular Docking Simulation, Neoplasms pathology, Protein Binding, Alkynes chemistry, Antineoplastic Agents pharmacology, Copper metabolism, Neoplasms drug therapy, Phenylalanine chemistry, Phenylalanine pharmacology, Serum Albumin, Bovine metabolism
- Abstract
Herein, we described the synthesis of two L-phenylalanines α-derivatized with a terminal alkyne moiety whose structures differed by phenyl ring halogen substitution (two o-Cl in 1 vs. one p-Br in 2) and investigated their effect on biological macromolecules and living cells. We explored their interaction with quadruplex DNA (G4 DNA), using tel
26 and c-myc as models, and bovine serum albumin (BSA). By CD spectroscopy, we found that 1 caused minor tel26 secondary structure changes, leading also to a slight thermal stabilization of this hybrid antiparallel/parallel G4 structure, while the c-myc parallel topology remained essentially unchanged upon 1 binding. Other CD evidences showed the ability of 1 to bind BSA, while molecular docking studies suggested that the same molecule could be housed into the hydrophobic cavity between sub-domains IIA, IIB, and IIIA of the protein. Furthermore, preliminary aggregation studies, based on concentration-dependent spectroscopic experiments, suggested the ability of 1 to aggregate forming noncovalent polymeric systems in aqueous solution. Differently from 1, the bromine-modified compound was able to bind Cu(II) ion, likely with the formation of a CuL2 complex, as found by UV spectroscopy. Finally, cell tests excluded any cytotoxic effect of both compounds toward normal cells, but showed slight antiproliferative effects of 2 on PC3 cancerous cells at 24 h, and of 1 on both T98G and MDA-MB-231 cancer cells at 48 h.- Published
- 2020
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