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Permanent positive charge strongly influences DNA/RNA binding and antiproliferative activity of urea-phenanthridinium conjugates


Radić Stojković, Marijana; Marczi, Saška; Glavaš-Obrovac, Ljubica; Piantanida, Ivo
Permanent positive charge strongly influences DNA/RNA binding and antiproliferative activity of urea-phenanthridinium conjugates // European Journal of Medicinal Chemistry, 45 (2010), 8; 3281-3292 doi:10.1016/j.ejmech.2010.04.006 (međunarodna recenzija, članak, znanstveni)


Naslov
Permanent positive charge strongly influences DNA/RNA binding and antiproliferative activity of urea-phenanthridinium conjugates

Autori
Radić Stojković, Marijana ; Marczi, Saška ; Glavaš-Obrovac, Ljubica ; Piantanida, Ivo

Izvornik
European Journal of Medicinal Chemistry (0223-5234) 45 (2010), 8; 3281-3292

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

Ključne riječi
Urea-phenanthridinium; DNA; RNA; fluorescence selectivity; intercalation; antiproliferative activity

Sažetak
An introduction of the permanent positive charge by methylation of heterocyclic nitrogen on a series of previously studied bis-urea phenanthridine derivatives substantially changed their interactions with DNA and RNA as well as biological activity. At variance to non-methylated analogues, novel methylated derivatives interacted with DNA/RNA not only at pH 5 but also at pH 7, and some compounds switched DNA binding mode from minor groove binding (non-methylated derivatives) to intercalation (novel, methylated derivatives). Moreover, selective ds-RNA over ds-DNA thermal stabilisation of previously observed non-methylated derivatives was reversed for novel, methylated derivatives. The variation of linker length connecting two urea-phenanthridinium conjugates regulated their binding modes toward double stranded polynucleotides. All novel compounds were able to distinguish between polynucleotides of A-T(U) and G-C basepair composition by specific fluorescence change. Moreover, the introduction of permanent positive charge on the phenanthridinium moiety resulted in significantly higher biological potency in respect to non-methylated analogues.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
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, )

Ustanove
Institut "Ruđer Bošković", Zagreb,
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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