2. Academic Validation
  3. Novel modified leucine and phenylalanine dipeptides modulate viability and attachment of cancer cells

Novel modified leucine and phenylalanine dipeptides modulate viability and attachment of cancer cells

  • Eur J Med Chem. 2020 Feb 15;188:112036. doi: 10.1016/j.ejmech.2020.112036.
Radek Jorda 1,  Pratibha Magar 2,  Denisa Hendrychová 3,  Karel Pauk 2,  Michal Dibus 4,  Eliška Pilařová 2,  Aleš Imramovský 5,  Vladimír Kryštof 6
Affiliations

Affiliations

  • 1 Laboratory of Growth Regulators, Palacky University & Institute of Experimental Botany, The Czech Academy of Sciences, Šlechtitelů 27, 78371, Olomouc, Czech Republic; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 5, 77900, Olomouc, Czech Republic.
  • 2 Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 95, 532 10, Pardubice, Czech Republic.
  • 3 Laboratory of Growth Regulators, Palacky University & Institute of Experimental Botany, The Czech Academy of Sciences, Šlechtitelů 27, 78371, Olomouc, Czech Republic.
  • 4 Department of Cell Biology, Charles University, Viničná 7, 12800, Prague, Czech Republic; Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University (BIOCEV), Průmyslová 595, 25242, Vestec u Prahy, Czech Republic.
  • 5 Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 95, 532 10, Pardubice, Czech Republic. Electronic address: [email protected].
  • 6 Laboratory of Growth Regulators, Palacky University & Institute of Experimental Botany, The Czech Academy of Sciences, Šlechtitelů 27, 78371, Olomouc, Czech Republic; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 5, 77900, Olomouc, Czech Republic. Electronic address: [email protected].
PMID: 31931341 DOI: 10.1016/j.ejmech.2020.112036
Abstract

Here, we describe the synthesis and biological characterization of 32 novel phenylalanine and leucine dipeptides modified on both the N and C termini by salicylic acid and aromatic or alicyclic amines, respectively. All compounds displayed antiproliferative activity in the tested Cancer cell lines and eight of the compounds exhibited single digit micromolar GI50 values. Treated cells rapidly detached from surface of tissue culture dishes and we found that focal adhesion kinase (FAK), p130CAS and paxillin, which are important regulators of cell adhesion, were dephosphorylated at Y397, Y410 and Y118, respectively. The most potent compound reduced proliferation in the HCT-116 cell line in a dose-dependent manner, as shown by a decrease in 5-bromo-2'-deoxyuridine incorporation into DNA. Furthermore, this compound increased the levels of several apoptotic markers, including activated caspases, and increased site-specific poly-(ADP-ribose)polymerase (PARP) cleavage.

Keywords

Adhesion; Apoptosis; Detachment; Dipeptide; cytotoxicity.

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