Evaluation of complexes of DNA duplexes and novel benzoxazoles or benzimidazoles by electrospray ionization mass spectrometry.
Electrospray ionization mass spectrometry is used to compare the metal ion binding and metal-mediated DNA binding of benzoxazole (1, 2, 3, 4) and benzimidazole (5) compounds and to elucidate the putative binding modes and stoichiometries. The observed metal versus non-metal-mediated DNA binding, as well as the specificity of DNA binding, is correlated with the biological activities of the analogs. The ESI-MS spectra for the antibacterial benzoxazole and benzimidazole analogs 4 and 5 demonstrated non-specific and non-metal-mediated binding to DNA, with the appearance of DNA complexes containing multiple ligands. The anticancer analog 2 demonstrates a clear preference for metal-mediated DNA interactions, with an apparent selectivity for Ni2+ -mediated binding over the more physiologically relevant Mg2+ or Zn2+ cations. Complexation between DNA and the biologically inactive analog 1 was not observed, either in the absence or presence of metal cations.
Oehlers
Leon
L
Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712-0165, USA.
Mazzitelli
Carolyn L
CL
Brodbelt
Jennifer S
JS
Rodriguez
Mireya
M
Kerwin
Sean
S
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry*; D001562:Benzimidazoles / Q000737:chemistry*; D001583:Benzoxazoles / Q000737:chemistry*; D001665:Binding Sites; D002412:Cations / Q000737:chemistry; D018736:DNA Adducts / Q000737:chemistry*; D008670:Metals / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D001583:Benzoxazoles; D002412:Cations; D018736:DNA Adducts; D008670:Metals; C082787:UK 1