A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Novel modified leucine and phenylalanine dipeptides modulate viability and attachment of cancer cells
Tekijät: Jorda R, Magar P, Hendrychova D, Pauk K, Dibus M, Pilarova E, Imramovsky A, Krystof V
Kustantaja: ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Julkaisuvuosi: 2020
Journal: European Journal of Medicinal Chemistry
Tietokannassa oleva lehden nimi: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Lehden akronyymi: EUR J MED CHEM
Artikkelin numero: 112036
Vuosikerta: 188
Sivujen määrä: 13
ISSN: 0223-5234
DOI: https://doi.org/10.1016/j.ejmech.2020.112036
Tiivistelmä
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 anti proliferative activity in the tested cancer cell lines and eight of the compounds exhibited single digit micromolar GI(50) 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. (C) 2020 Elsevier Masson SAS. All rights reserved.
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 anti proliferative activity in the tested cancer cell lines and eight of the compounds exhibited single digit micromolar GI(50) 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. (C) 2020 Elsevier Masson SAS. All rights reserved.
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