title: Interaction of Di-2-pyridylketone 2-pyridine Carboxylic Acid Hydrazone and Its Copper Complex with BSA: Effect on Antitumor Activity as Revealed by Spectroscopic Studies.
abstract: The drug, di-2-pyridylketone-2-pyridine carboxylic acid hydrazone (DPPCAH) and its copper complex (DPPCAH-Cu) exhibit significant antitumor activity. However, the mechanism of their pharmacological interaction with the biological molecule bovine serum albumin (BSA) remains poorly understood. The present study elucidates the interactions between the drug and BSA through MTT assays, spectroscopic methods and molecular docking analysis. Our results indicate that BSA could attenuate effect on the cytotoxicity of DPPCAH, but not DPPCAH-Cu. Data from fluorescence quenching measurements demonstrated that both DPPCAH and DPPCAH-Cu could bind to BSA, with a reversed effect on the environment of tryptophan residues in polarity. CD spectra revealed that the DPPCAH-Cu exerted a slightly stronger effect on the secondary structure of BSA than DPPCAH. The association constant of DPPCAH with BSA was greater than that of DPPCAH-Cu. Docking studies indicated that the binding of DPPCAH to BSA involved a greater number of hydrogen bonds compared to DPPCAH-Cu. The calculated distances between bound ligands and tryptophans in BSA were in agreement with fluorescence resonance energy transfer results. Thus, the binding affinity of the drug (DPPCAH or DPPCAH-Cu) with BSA partially contributes to its antitumor activity; the greater the drug affinity is to BSA, the less is its antitumor activity.
authors.affiliation: Department of Molecular Biology &amp; Biochemistry, Xinxiang Medical University, Xinxiang 453003, Henan, China. lcp831220@163.com.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Molecular Biology &amp; Biochemistry, Xinxiang Medical University, Xinxiang 453003, Henan, China. htengfei@yahoo.com.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Molecular Biology &amp; Biochemistry, Xinxiang Medical University, Xinxiang 453003, Henan, 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, Henan, 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, Henan, 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, Henan, China. qizhangyang0324@163.com.
authors.forename: Zhangyang
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Department of Molecular Biology &amp; Biochemistry, Xinxiang Medical University, Xinxiang 453003, Henan, China. changzhenl@yahoo.com.|Henan Collaborative Innovation Center of Molecular Diagnostics and Laboratory Medicine, Xinxiang 453003, Henan, China. changzhenl@yahoo.com.
authors.forename: Changzheng
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D006835:Hydrazones / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012710:Serum Albumin, Bovine / Q000737:chemistry* / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
chemical_list: D000970:Antineoplastic Agents; D006835:Hydrazones; D012710:Serum Albumin, Bovine; D003300:Copper
keywords: FRET; copper complex; di-2-pyridylketone 2-pyridine carboxylic acid hydrazone; fluorescence; molecular docking