Crystal structures and study of interaction mode of bis-b enzimidazole-b enzene derivatives with DNA

作者：Valdes-Garcia, Josue; Viviano-Po***as, Alejandro O.; Rivera-Chavez, Jose; Ramirez-Apan, Teresa; Martinez-Vargas, Sergio; Aguirre-Hernandez, Eva; German-Acacio, Juan M.; Morales-Morales, David; Dorazco-Gonzalez, Alejandro^*

来源：Journal of Molecular Structure, 2022, 1249: 131582.

DOI：10.1016/j.molstruc.2021.131582

• HUMAN SERUM-ALBUMIN
• BENZIMIDAZOLE DERIVATIVES
• CYTOTOXIC ACTIVITIES
• MINOR-GROOVE
• BINDING
• ANTICANCER
• FLUORESCENCE
• IMIDAZOLE
• RECOGNITION
• BISQUINOLINIUM

Three derivatives of the scaffold, 1,3-bis(benzimidazol-2-yl)benzene 1-3 , were synthesized and structurally characterized by single X-ray diffraction. Spectroscopic studies by fluorescence competitive displacement assays, UV-Vis, circular dichroism, and docking simulations revealed that the interaction of these derivatives with ds-DNA at pH = 7.4 is through groove binding mode with pronounced affinity to derivative 1 which contains hydrogen bond donor groups (NH), 1 (K-A = 4.48 x 10(4) M-1), over the other derivatives lacking hydrogen bond donors, 2-3 (K-A = 6.6 x 10 x 2.1 x 10(3) M-1). Melting DNA studies and Stern-Volmer constants at different temperatures of 1 with DNA are consistent with a static quenching mechanism by a groove binding mode. Based on experimentally estimated enthalpic (A(H) = 55.33 kJmol(-1)) and entropic (Delta S = 98.77 Jmol(-1) K-1) parameters, and theoretical calculations for the complex 1-DNA, the proposed interaction model is predominantly enthalpically driven through hydrogen bonds and Van der Waals.
Finally, bisbenzimidazole derivatives 1 and 2 exhibit potential anti-proliferative activity toward human colorectal adenocarcinoma and human lung adenocarcinoma, respectively.