Pregled bibliografske jedinice broj: 642490
Biological activity and DNA binding studies of 2-substituted benzimidazo[1,2-a]quinolines bearing different amino side chains
Biological activity and DNA binding studies of 2-substituted benzimidazo[1,2-a]quinolines bearing different amino side chains // MedChemComm, 4 (2013), 12; 1537-1550 doi:10.1039/c3md00193h (međunarodna recenzija, članak, znanstveni)
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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), 12;
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
Projekti:
MZOS-098-0982464-2514 - Uloga različitih mehanizama odgovora stanica na terapiju oštećenjem DNA (Kralj, Marijeta, MZOS ) ( CroRIS)
MZOS-125-0982464-1356 - Novi heterocikli kao antitumorski i antivirusni (pametni) lijekovi (Hranjec, Marijana, MZOS ) ( CroRIS)
Ustanove:
Institut "Ruđer Bošković", Zagreb,
Fakultet kemijskog inženjerstva i tehnologije, Zagreb
Profili:
Grace Karminski-Zamola
(autor)
Marijeta Kralj
(autor)
Irena Martin-Kleiner
(autor)
Oliver Vugrek
(autor)
Marijana Hranjec
(autor)
Nataša Perin
(autor)
Citiraj ovu publikaciju:
Časopis indeksira:
- Web of Science Core Collection (WoSCC)
- Science Citation Index Expanded (SCI-EXP)
- SCI-EXP, SSCI i/ili A&HCI
- Scopus
Uključenost u ostale bibliografske baze podataka::
- CA Search (Chemical Abstracts)