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Pregled bibliografske jedinice broj: 642490

Biological activity and DNA binding studies of 2-substituted benzimidazo[1, 2-a]quinolines bearing different amino side chains


Perin, Nataša; Martin-Kleiner, Irena; Nhili, Raja; Laine, William; David-Cordonnier, Marie-Hélène; Vugrek, Oliver; Karminski-Zamola, Grace; Kralj, Marijeta; Hranjec, Marijana
Biological activity and DNA binding studies of 2-substituted benzimidazo[1, 2-a]quinolines bearing different amino side chains // MedChemComm, 4 (2013), 1537-1550 doi:10.1039/c3md00193h (međunarodna recenzija, članak, znanstveni)


Naslov
Biological activity and DNA binding studies of 2-substituted benzimidazo[1, 2-a]quinolines bearing different amino side chains

Autori
Perin, Nataša ; Martin-Kleiner, Irena ; Nhili, Raja ; Laine, William ; David-Cordonnier, Marie-Hélène ; Vugrek, Oliver ; Karminski-Zamola, Grace ; Kralj, Marijeta ; Hranjec, Marijana

Izvornik
MedChemComm (2040-2503) 4 (2013); 1537-1550

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

Ključne riječi
Benzimidazoles ; benzimidazo[1 ; 2-a]quinolines ; amino side chains ; antiproliferative activity ; DNA binding properties

Sažetak
This manuscript describes the synthesis and biological activity of 2-substituted benzimidazo[1, 2-a]quinolines substituted with different amino side chains on quinoline nuclei prepared by microwave assisted amination. The majority of compounds were newly synthesized and active in the submicromolar IC50 concentrations, while the alkylamino substituents, either aliphatic or cyclic, increased antitumor activities in comparison with previously published nitro and amino substituted benzimidazo[1, 2-a]quinolines. The compound with the longest tertiary amino side chain 16 was the least active. A series of additional experiments, including DNA binding propensities, topoisomerases I and II inhibition, inhibition of recombinant green fluorescent protein in a cell-free translation system, cell cycle perturbances and cellular localization, was performed to shed more light on the mechanisms of action of the most active ones. The DNA intercalation activity correlates with anti-proliferative effect. Several DNA intercalators (11, 20 and 21) also evidence some sequence selective DNA binding. However, only N, N-dimethylaminopropyl analogue 11 was unequivocally demonstrated to be a strong DNA-binder and intercalative agent, which efficiently targets DNA in the cells, while the activity of compound 10, with bulky i-butyl amino side chain, points to its potential antimitotic activity.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
098-0982464-2514 - Uloga različitih mehanizama odgovora stanica na terapiju oštećenjem DNA (Marijeta Kralj, )
125-0982464-1356 - Novi heterocikli kao antitumorski i antivirusni ("pametni") lijekovi (Marijana Hranjec, )

Ustanove
Institut "Ruđer Bošković", Zagreb,
Fakultet kemijskog inženjerstva i tehnologije, Zagreb

Časopis indeksira:


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


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