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Synthesis, DNA/RNA affinity and antitumour activity of new aromatic diamidines linked by 3, 4-ethylenedioxythiophene


Stolić, Ivana; Mišković, Katarina; Piantanida, Ivo; Baus Lončar, Mirela; Glavaš-Obrovac, Ljubica; Bajić, Miroslav
Synthesis, DNA/RNA affinity and antitumour activity of new aromatic diamidines linked by 3, 4-ethylenedioxythiophene // European journal of medicinal chemistry, 46 (2011), 2; 743-755 doi:10.1016/j.ejmech.2010.12.010 (međunarodna recenzija, članak, znanstveni)


Naslov
Synthesis, DNA/RNA affinity and antitumour activity of new aromatic diamidines linked by 3, 4-ethylenedioxythiophene

Autori
Stolić, Ivana ; Mišković, Katarina ; Piantanida, Ivo ; Baus Lončar, Mirela ; Glavaš-Obrovac, Ljubica ; Bajić, Miroslav

Izvornik
European journal of medicinal chemistry (0223-5234) 46 (2011), 2; 743-755

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

Ključne riječi
Diphenylamidine; 3; 4-ethylenedioxythiophene; DNA/RNA binding; antitumour activity

Sažetak
A series of novel 2, 5-bis(amidinophenyl)-3, 4-ethylenedioxythiophenes (5-10 and 15) has been synthesized. Compounds 5-10 bind to the DNA minor groove as the dominant binding site and strongly stabilize the double helix of ct-DNA. Surprisingly, the same compounds also thermally stabilize ds-RNA, whereby most of them form stacked dimers along the RNA double helix. The only exception is compound 15 which, due to its structural features, showed no interaction with DNA or RNA. Compounds 5-10 have shown a moderate to strong cytotoxic effect (GI50 = 1.5-9.0 µM) on a panel of seven tumour cell lines. The diimidazoline derivative 9, due to its highest inhibitory potential on the growth of all tested tumour cell lines, was investigated in more detail by testing its ability to enter into cells and influence the cell cycle. Compound 9 (5 µM) was internalized successfully in cell cytoplasm during a 30-min incubation period, followed by nuclear localization upon 90-min incubation. Significant arrest in HeLa cells in the G2/M phase, shown by cell cycle analysis at an equitoxic (50 µM) concentration, suggests interaction of a studied compound with cellular DNA as the main mode of biological action.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
053-0982914-2965 - Dizajn i sinteza bisamidina sa protutumorskim djelovanjem (Miroslav Bajić, )
098-0982914-2918 - Dizajn, sinteza i ispitivanje interakcija malih molekula s DNA, RNA i proteinima (Ivo Piantanida, )
219-0982914-2176 - Mehanizam bioloških učinaka novih malih molekula na stanice tumora čovjeka (Ljubica Glavaš Obrovac, )
219-0982914-2179 - Uloga malih zaštitinih TFF proteina u zdravlju i bolesti (Tatjana Belovari, )

Ustanove
Veterinarski fakultet, Zagreb,
Institut "Ruđer Bošković", Zagreb,
Klinički bolnički centar Osijek,
Medicinski fakultet, Osijek

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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