title: Insight into the interaction of antitubercular and anticancer compound clofazimine with human serum albumin: spectroscopy and molecular modelling.
abstract: The binding of clofazimine to human serum albumin (HSA) was investigated by applying optical spectroscopy and molecular docking methods. Fluorescence quenching data revealed that clofazimine binds to protein with binding constant in the order of 104M-1, and with the increase in temperature, Stern-Volmer quenching constants gradually decreased indicating quenching mode to be static. The UV-visible spectra showed increase in absorbance upon interaction of HSA with clofazimine which further reveals formation of the drug-albumin complex. Thermodynamic parameters obtained from fluorescence data indicate that the process is exothermic and spontaneous. Forster distance (Ro) obtained from fluorescence resonance energy transfer is found to be 2.05 nm. Clofazimine impelled rise in α-helical structure in HSA as observed from far-UV CD spectra while there are minor alterations in tertiary structure of the protein. Clofazimine interacts strongly with HSA inducing secondary structure in the protein and slight alterations in protein topology as suggested by dynamic light scattering results. Moreover, docking results indicate that clofazimine binds to hydrophobic pocket near to the drug site II in HSA.
authors.affiliation: a Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh 202002 , India.
authors.forename: Mohammad Rehan
authors.initials: MR
authors.lastname: Ajmal
authors.affiliation: a Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh 202002 , India.
authors.forename: Nida
authors.initials: N
authors.lastname: Zaidi
authors.affiliation: a Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh 202002 , India.
authors.forename: Parvez
authors.initials: P
authors.lastname: Alam
authors.affiliation: a Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh 202002 , India.
authors.forename: Saima
authors.initials: S
authors.lastname: Nusrat
authors.affiliation: a Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh 202002 , India.
authors.forename: Mohd Khursheed
authors.initials: MK
authors.lastname: Siddiqi
authors.affiliation: b Laboratory of Immunology and Molecular Physiology, Zoology Department, Faculty of Science , Assiut University , 71516 Assiut , Egypt.
authors.forename: Gamal
authors.initials: G
authors.lastname: Badr
authors.affiliation: c Deanship of Scientific Research , King Saud University , Riyadh , Saudi Arabia.|d Food Science and Nutrition Department , National Research Center , Dokki, Cairo , Egypt.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Mahmoud
authors.affiliation: a Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh 202002 , India.
authors.forename: Rizwan Hasan
authors.initials: RH
authors.lastname: Khan
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D000995:Antitubercular Agents / Q000737:chemistry*; D001665:Binding Sites; D002942:Circular Dichroism; D002991:Clofazimine / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013057:Spectrum Analysis
chemical_list: D000970:Antineoplastic Agents; D000995:Antitubercular Agents; D012709:Serum Albumin; D002991:Clofazimine
keywords: HSA; binding; clofazimine; fluorescence; molecular docking