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.

Correction: Zhongjie Xu, et al. Analysis of the Interaction of Dp44mT with Human Serum Albumin and Calf Thymus DNA using Molecular Docking and Spectroscopic Techniques. Int. J. Mol. Sci. 2016, 17, 1042

“…As a result of a recent letter to the editor [1], we would like to make several corrections to our manuscript [2]. …”

Letter to the Editor: “Analysis of the Interaction of Dp44mT with Human Serum Albumin and Calf Thymus DNA Using Molecular Docking and Spectroscopic Techniques”

“…In reading the article by Xu, Z., et al entitled “Analysis of the Interaction of Dp44mT with Human Serum Albumin and Calf Thymus DNA Using Molecular Docking and Spectroscopic Techniques” [1], there is evidence that some of the key methods and comparisons utilized in this study are non-optimal and problematic.…”

Editorial: Analysis of the Interaction of Dp44mT with Human Serum Albumin and Calf Thymus DNA Using Molecular Docking and Spectroscopic Techniques

“…In a recent Internal Journal of the Molecular Sciences ( IJMS ) publication, Xu and co-workers presented evidence on the pharmacological interaction of the anti-tumor agent di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) with human serum albumin (HSA) and DNA [1]. The pharmacological interaction of Dp44mT is an important issue in the optimization of Dp44mT as an anti-tumor agent [2].…”

“…Furthermore, the performed measurements were perceived as non-optimal and potentially problematic, and thus, the results and their interpretation might be unreliable. Because IJMS takes any complaint that is brought before us serious, IJMS started an investigation and asked Xu et al to reply to the letter in detail [4] and assigned independent experts to reevaluate the manuscript and the correspondence regarding this manuscript. In addition, we, as members of the editorial board, evaluated the issues brought before us.…”

“…We feel that the paper by Xu et al provides new insights into the pharmacological action of Dp44mT and fits well within a climate that allows and stimulates scientific discussion. Nonetheless, two issues raised in the letter to the editor [3] were identified that required correction/amendment, which are published in a corrigendum [5]. …”