Evaluation of complexes of DNA duplexes and novel benzoxazoles or benzimidazoles by electrospray ionization mass spectrometry.

Journal article

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.

Authors: Oehlers, L; Mazzitelli, C; Brodbelt, J; Rodriguez, M; Kerwin, S

• Publication status: Published
• Journal: Journal of the American Society for Mass Spectrometry
• Volume: 15
• Issue: 11
• Pages: 1593-1603
• Publication date: 2004-11-01
• DOI: 10.1016/j.jasms.2004.07.015
• EISSN: 1879-1123
• ISSN: 1044-0305
• Language: English
• Keywords: Spectrometry, Mass, Electrospray Ionization; DNA Adducts; Benzimidazoles; Anti-Bacterial Agents; Cations; Binding Sites; Benzoxazoles; Metals; Antineoplastic Agents