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New Quinoline-Arylamidine Hybrids : Synthesis, DNA/RNA Binding and Antitumor Activity


Krstulović, Luka; Stolić, Ivana; Jukić, Marijana; Opačak-Bernardi, Teuta; Starčević, Kristina; Bajić, Miroslav; Glavaš-Obrovac, Ljubica
New Quinoline-Arylamidine Hybrids : Synthesis, DNA/RNA Binding and Antitumor Activity // European journal of medicinal chemistry, 137 (2017), 196-210 doi:10.1016/j.ejmech.2017.05.054 (međunarodna recenzija, članak, znanstveni)


Naslov
New Quinoline-Arylamidine Hybrids : Synthesis, DNA/RNA Binding and Antitumor Activity

Autori
Krstulović, Luka ; Stolić, Ivana ; Jukić, Marijana ; Opačak-Bernardi, Teuta ; Starčević, Kristina ; Bajić, Miroslav ; Glavaš-Obrovac, Ljubica

Izvornik
European journal of medicinal chemistry (0223-5234) 137 (2017); 196-210

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

Ključne riječi
Hybrid molecule, 7-Chloroquinoline, Aromatic amidine, DNA/RNA binding, Antitumor activity

Sažetak
Four series of new hybrid molecules with 7-chloroquinoline and arylamidine moieties joined through the rigid -O- (groups I (2a-g) and II (5a-g)) or flexible -NH-CH2-CH2-O- (groups III (8a-g) and IV (10a-g)) linker were synthesized, and their DNA/RNA binding properties and cytotoxic activity were tested, against several human cancer lines. The compounds and their interaction with DNA and RNA were studied by UV-Vis and CD spectroscopy. The obtained results showed that the binding affinity of the investigated compounds increases proportionally with the increase of the length and number of groups able to form hydrogen bonds with ds-polynucleotides. Improvement of binding was additionally achieved by reduction of the structural rigidity of the investigated compounds, new hybrid compounds preferentially bind to ctDNA. For most of them the DNA/RNA grooves are dominant binding sites, except for the compounds from group II for which intercalation in polyA-polyU was the dominant binding mode. The antiproliferative effects were tested by the MTT test on normal (MDCK1), carcinoma (HeLa and CaCo2) and leukemia cell lines (Raji and K462). The GI50 values for all investigated compounds ranged from 5 to more than 100 × 10-6 mol dm-3. Carcinoma cells were more resistant to the investigated compounds than leukemia cells. The most effective compounds against leukemia cell lines were from group IV (10a-g), with GI50 values ranging from of 5 and 35 × 10-6 mol dm-3. The cell cycle arrest was investigated by flow cytometry and the obtained results indicate that the selected compounds, 2d, 2e, 8a, 10d, 10e, and 10f, induce changes in the cell cycle of treated cells, but the cycle phase distribution varies between them. A significant decrease in the number of cells in S phase (p < 0.001) was observed in all treated cells, but only 10d and 10f induce cell cycle arrest at G0/G1 phase, dominantly.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Temeljne medicinske znanosti

Citiraj ovu publikaciju

Krstulović, Luka; Stolić, Ivana; Jukić, Marijana; Opačak-Bernardi, Teuta; Starčević, Kristina; Bajić, Miroslav; Glavaš-Obrovac, Ljubica
New Quinoline-Arylamidine Hybrids : Synthesis, DNA/RNA Binding and Antitumor Activity // European journal of medicinal chemistry, 137 (2017), 196-210 doi:10.1016/j.ejmech.2017.05.054 (međunarodna recenzija, članak, znanstveni)
Krstulović, L., Stolić, I., Jukić, M., Opačak-Bernardi, T., Starčević, K., Bajić, M. & Glavaš-Obrovac, L. (2017) New Quinoline-Arylamidine Hybrids : Synthesis, DNA/RNA Binding and Antitumor Activity. European journal of medicinal chemistry, 137, 196-210 doi:10.1016/j.ejmech.2017.05.054.
@article{article, year = {2017}, pages = {196-210}, DOI = {10.1016/j.ejmech.2017.05.054}, keywords = {Hybrid molecule, 7-Chloroquinoline, Aromatic amidine, DNA/RNA binding, Antitumor activity}, journal = {European journal of medicinal chemistry}, doi = {10.1016/j.ejmech.2017.05.054}, volume = {137}, issn = {0223-5234}, title = {New Quinoline-Arylamidine Hybrids : Synthesis, DNA/RNA Binding and Antitumor Activity}, keyword = {Hybrid molecule, 7-Chloroquinoline, Aromatic amidine, DNA/RNA binding, Antitumor activity} }

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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