Synthesis of phenanthridinium-bis-nucleobase conjugates, interactions with poly U, nucleotides and in vitro antitumour activity of mono- and bis-nucleobase conjugates.
Novel bis-nucleobase-phenanthridinium conjugates were synthesised and their aqueous solutions spectroscopically characterised. Bis-adenine conjugate revealed in aqueous solutions significantly more pronounced intramolecular aromatic stacking interactions than bis-uracil analogue. In contrast with previously reported poly A recognition by bis-uracil conjugate, recognition of complementary nucleotides and poly U was not observed due to the strong interference of bulk water with hydrogen bonding between nucleobases. The screening of anticancer activity on six human cell lines revealed that tethering of a nucleobase to phenanthridinium moiety diminished antiproliferative potential of phenanthridinium. However, among mono-nucleobase conjugates adenine derivative was found to be the most selective one (MiaPaCa-2, Hep-2).
Tumir
L-M
LM
Laboratory of Supramolecular and Nucleoside Chemistry, Division of Organic Chemistry and Biochemistry, Ruder Bosković Institute, Bijenicka 54, HR 10002 Zagreb, P.O.B. 180, Croatia.
Piantanida
I
I
Zinić
M
M
Juranović Cindrić
I
I
Meić
Z
Z
Kralj
M
M
Tomić
S
S
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D006367:HeLa Cells; D006801:Humans; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D015394:Molecular Structure; D009711:Nucleotides / Q000737:chemistry*; D010617:Phenanthridines / Q000737:chemistry*; D011072:Poly U / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence / Q000379:methods; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013329:Structure-Activity Relationship; D013997:Time Factors
D000970:Antineoplastic Agents; D009711:Nucleotides; D010617:Phenanthridines; C014740:phenanthridinium; D011072:Poly U