The binding investigation of ziprasidone with calf thymus DNA by multiple spectrums and molecular docking

Ziprasidone (Zi) is a 2-indolone drug that has been recommended as first-line medication for schizophrenic treatment by major guides of China and America. In this paper, the binding mode of Zi and calf thymus (ctDNA) was investigated for the first time. Fluorescence spectrum studies preliminary verified that Zi bound to groove region of ctDNA. UV-vis spectra showed obvious hyperchromicity at 260 nm for ctDNA-Zi system compared to the absorption sum of ctDNA and Zi, which also could be concluded that the interaction mode of Zi to ctDNA was probably groove binding. In ¹H NMR of Zi, the addition of ctDNA had no influence on its spectrum, and the viscosity of ctDNA was also unaffected by the addition of Zi. These phenomenon proved once again that Zi interacted with ctDNA at groove region. Besides, molecular docking results reflected that Zi indeed bound to minor groove region of ctDNA with hydrogen bonds as main acting force. This study elaborated detailedly the groove binding mode of antipsychotic drug Zi interacting with ctDNA, and provided effective information for the design and development of new-type antipsychotic drugs.