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Novel Phenyl and Pyridyl Substituted Derivatives of Isoindolines: Synthesis, Antitumor Activity and DNA binding features


Sović, Irena; Kraljević Pavelić, Sandra; Markova-Car, Elitza; Ilić, Nataša; Nhili, Raja; Depauw, Sabine; David-Cordonnier, Marie-Hélène; Karminski-Zamola, Grace
Novel Phenyl and Pyridyl Substituted Derivatives of Isoindolines: Synthesis, Antitumor Activity and DNA binding features // European journal of medicinal chemistry, 87 (2014), 24; 372-385 doi:10.1016/j.ejmech.2014.09.079 (međunarodna recenzija, članak, znanstveni)


Naslov
Novel Phenyl and Pyridyl Substituted Derivatives of Isoindolines: Synthesis, Antitumor Activity and DNA binding features

Autori
Sović, Irena ; Kraljević Pavelić, Sandra ; Markova-Car, Elitza ; Ilić, Nataša ; Nhili, Raja ; Depauw, Sabine ; David-Cordonnier, Marie-Hélène ; Karminski-Zamola, Grace

Izvornik
European journal of medicinal chemistry (0223-5234) 87 (2014), 24; 372-385

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Heterocyclic compounds; phenyl and pyridyl substituted isoindolines; antiproliferative activity; DNA binding; intercalator; sequence-selective binding.

Sažetak
Novel phenyl-substituted (3a-3d, 4a, 5, 8a, 8b and 9a) and pyridyl-substituted (3e-3i, 4b, 8c-8e, 9b and 9c) isoindolines are prepared in the reaction of o-phthalaldehyde and corresponding substituted aromatic and heteroaromatic amines by modification of reaction conditions from low to high temperature and from neutral to acidic environment. The antiproliferative activity of some prepared substituted isoindolines was assessed on a panel of tumor cell lines and human fibroblasts. The majority of tested compounds was active at the highest tested concentrations where phenyl-substituted isoindolines 3a and 3b and pyridine-substituted isoindoline 3g showed a selective effect at micromolar concentrations on HepG2 cell line in comparison with other tested tumor cell lines and normal human fibroblasts. The strongest yet non-selective effect was observed for the pyridyl-substituted isoindoline 8c. Their mechanism of action on tumor cell death induction was however different as compounds 3a and 8c probably induced mitotic catastrophe while compound 3b induced apoptosis. Indeed, DNA binding properties evidenced that compounds 8a, 8c and 8d bind to DNA as highly potent DNA intercalators. By contrast, compounds 3b, 3e, 3i, 4a and 5 did not target the DNA. At last, the phenyl-substituted compound 8b proved to be a strong DNA binding compound with sequence selective binding and without DNA intercalation profile.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija



POVEZANOST RADA


Projekt / tema
125-0982464-1356 - Novi heterocikli kao antitumorski i antivirusni ("pametni") lijekovi (Marijana Hranjec, )
335-0000000-3532 - Uloga IGF2 i signalni putovi nizvodno u karcinomima pluća čovjeka (Sandra Kraljević Pavelić, )

Ustanove
Medicinski fakultet, Rijeka,
Fakultet kemijskog inženjerstva i tehnologije, Zagreb,
Sveučilište u Rijeci - Odjel za biotehnologiju

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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