Dacarbazine as a minor groove binder of DNA: Spectroscopic, biophysical and molecular docking studies.
A detailed investigation on the mode of action and binding mechanism of a potent anticancer drug, 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DCR) with calf thymus DNA (ctDNA) was carried out. UV-vis and fluorescence spectrophotometry suggested the formation of complex between DCR and ctDNA. The binding constant (Kb) determined by ITC was 7.89×10(4) M(-1). Thermodynamic parameters obtained by isothermal calorimetry suggested the spontaneous free energy (ΔG<0) and large favorable enthalpy driven (ΔH<0) reaction, indicating the key role of hydrogen bonding and van der Waals forces in groove binding process. Moreover, DNA-melting and circular dichroism as well as competitive displacement studies with ethidium bromide, Hoechst 33258 and potassium iodide, clearly established the formation of a groove binding system between the DCR and ctDNA. Molecular docking analysis further confirmed DCR to be a minor groove binder involving hydrogen bonding mediated 'A-T'-rich region of 'B-DNA'.
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, U.P. 202002, India.
Irshad
I
Ahmad
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, U.P. 202002, India. Electronic address: masoodamua@rediffmail.com.
Masood
M
Ahmad
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry*; D001667:Binding, Competitive; D006690:Bisbenzimidazole / Q000737:chemistry; D002417:Cattle; D004247:DNA / Q000737:chemistry*; D059371:DNA, B-Form / Q000737:chemistry*; D003606:Dacarbazine / Q000737:chemistry*; D004996:Ethidium / Q000737:chemistry; D006860:Hydrogen Bonding; D007364:Intercalating Agents / Q000737:chemistry*; D007700:Kinetics; D062105:Molecular Docking Simulation; D011193:Potassium Iodide / Q000737:chemistry; D013816:Thermodynamics
D018906:Antineoplastic Agents, Alkylating; D059371:DNA, B-Form; D007364:Intercalating Agents; D011193:Potassium Iodide; D003606:Dacarbazine; D004247:DNA; C427203:calf thymus DNA; D004996:Ethidium; D006690:Bisbenzimidazole
Calf thymus DNA; Dacarbazine; Molecular docking