title: Analysis of the Interaction of Dp44mT with Human Serum Albumin and Calf Thymus DNA Using Molecular Docking and Spectroscopic Techniques.
abstract: Di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT) exhibits significant antitumor activity. However, the mechanism of its pharmacological interaction with human serum albumin (HSA) and DNA remains poorly understood. Here, we aimed to elucidate the interactions of Dp44mT with HSA and DNA using MTT assays, spectroscopic methods, and molecular docking analysis. Our results indicated that addition of HSA at a ratio of 1:1 did not alter the cytotoxicity of Dp44mT, but did affect the cytotoxicity of the Dp44mT-Cu complex. Data from fluorescence quenching and UV-VIS absorbance measurements demonstrated that Dp44mT could bind to HSA with a moderate affinity (Ka = approximately 10⁴ M(-1)). CD spectra revealed that Dp44mT could slightly disrupt the secondary structure of HSA. Dp44mT could also interact with Ct-DNA, but had a moderate binding constant (KEB = approximately 10⁴ M(-1)). Docking studies indicated that the IB site of HSA, but not the IIA and IIIA sites, could be favorable for Dp44mT and that binding of Dp44mT to HSA involved hydrogen bonds and hydrophobic force, consistent with thermodynamic results from spectral investigations. Thus, the moderate binding affinity of Dp44mT with HSA and DNA partially contributed to its antitumor activity and may be preferable in drug design approaches.
authors.affiliation: College of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, China. xcj029@163.com.
authors.forename: Zhongjie
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Molecular Biology &amp; Biochemistry, Xinxiang Medical University, Xinxiang 453003, China. liuyouxun@126.com.
authors.forename: Youxun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Molecular Biology &amp; Biochemistry, Xinxiang Medical University, Xinxiang 453003, China. sufengzhou@xxmu.edu.cn.
authors.forename: Sufeng
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Molecular Biology &amp; Biochemistry, Xinxiang Medical University, Xinxiang 453003, China. fuyun9801@163.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Molecular Biology &amp; Biochemistry, Xinxiang Medical University, Xinxiang 453003, China. changzhengli@xxmu.edu.cn.|Henan Collaborative Innovation Center of Molecular Diagnostics and Laboratory Medicine, Xinxiang 453003, China. changzhengli@xxmu.edu.cn.
authors.forename: Changzheng
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000737:chemistry / Q000633:toxicity; D003300:Copper / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D013882:Thiosemicarbazones / Q000737:chemistry / Q000378:metabolism*
chemical_list: D056831:Coordination Complexes; D012709:Serum Albumin; D013882:Thiosemicarbazones; C539263:di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone; D003300:Copper; D004247:DNA; C427203:calf thymus DNA
keywords: Dp44mT; fluorescence quenching; molecular docking