title: Interaction of anticancer drug clofarabine with human serum albumin and human α-1 acid glycoprotein. Spectroscopic and molecular docking approach.
abstract: The binding interaction between clofarabine, an important anticancer drug and two important carrier proteins found abundantly in human plasma, Human Serum Albumin (HSA) and α-1 acid glycoprotein (AAG) was investigated by spectroscopic and molecular modeling methods. The results obtained from fluorescence quenching experiments demonstrated that the fluorescence intensity of HSA and AAG is quenched by clofarabine and the static mode of fluorescence quenching is operative. UV-vis spectroscopy deciphered the formation of ground state complex between anticancer drug and the two studied proteins. Clofarabine was found to bind at 298K with both AAG and HSA with the binding constant of 8.128×103and 4.120×103for AAG and HSA, respectively. There is stronger interaction of clofarabine with AAG as compared to HSA. The Gibbs free energy change was found to be negative for the interaction of clofarabine with AAG and HSA indicating that the binding process is spontaneous. Binding of clofarabine with HSA and AAG induced ordered structures in both proteins and lead to molecular compaction. Clofarabine binds to HSA near to drug site II. Hydrogen bonding and hydrophobic interactions were the main bonding forces between HSA-clofarabine and AAG-clofarabine as revealed by docking results. This study suggests the importance of binding of anticancer drug to AAG spatially in the diseases like cancers where the plasma concentration of AAG increases many folds. Design of drug dosage can be adjusted accordingly to achieve optimal treatment outcome.
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Mohammad Rehan
authors.initials: MR
authors.lastname: Ajmal
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Saima
authors.initials: S
authors.lastname: Nusrat
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Parvez
authors.initials: P
authors.lastname: Alam
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Nida
authors.initials: N
authors.lastname: Zaidi
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Mohsin Vahid
authors.initials: MV
authors.lastname: Khan
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Masihuz
authors.initials: M
authors.lastname: Zaman
authors.affiliation: Molecular Biology Department, Genetic Engineering and Biotechnology Division, National Research Centre, Dokki, Cairo, Egypt.
authors.forename: Yasser E
authors.initials: YE
authors.lastname: Shahein
authors.affiliation: Deanship of Scientific Research, King Saud University, Riyadh, Saudi Arabia; Food Science and Nutrition Department, National Research Center, Dokki, Cairo, Egypt.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Mahmoud
authors.affiliation: Zoology Department, Faculty of Science, Assiut University, 71516 Assiut, Egypt.
authors.forename: Gamal
authors.initials: G
authors.lastname: Badr
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India. Electronic address: rizwanhkhan1@gmail.com.
authors.forename: Rizwan Hasan
authors.initials: RH
authors.lastname: Khan
mesh_terms: D000227:Adenine Nucleotides / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D001087:Arabinonucleosides / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D000077866:Clofarabine; D006801:Humans; D062105:Molecular Docking Simulation / Q000379:methods*; D011485:Protein Binding / Q000502:physiology; D017433:Protein Structure, Secondary; D012709:Serum Albumin / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D012709:Serum Albumin; D000077866:Clofarabine
keywords: Anticancer; Circular dichroism; Clofarabine; Fluorescence quenching; Human serum albumin; Human serum α-1 acid glycoprotein; Molecular docking