title: Caffeine and sulfadiazine interact differently with human serum albumin: A combined fluorescence and molecular docking study.
abstract: The interaction and binding behavior of the well-known drug sulfadiazine (SDZ) and psychoactive stimulant caffeine (CAF) with human serum albumin (HSA) was monitored by in vitro fluorescence titration and molecular docking calculations under physiological condition. The quenching of protein fluorescence on addition of CAF is due to the formation of protein-drug complex in the ground state; whereas in case of SDZ, the experimental results were explained on the basis of sphere of action model. Although both these compounds bind preferentially in Sudlow's site 1 of the protein, the association constant is approximately two fold higher in case of SDZ (∼4.0×10(4)M(-1)) in comparison with CAF (∼9.3×10(2)M(-1)) and correlates well with physico-chemical properties like pKa and lipophilicity of the drugs. Temperature dependent fluorescence study reveals that both SDZ and CAF bind spontaneously with HSA. However, the binding of SDZ with the protein is mainly governed by the hydrophobic forces in contrast with that of CAF; where, the interaction is best explained in terms of electrostatic mechanism. Molecular docking calculation predicts the binding of these drugs in different location of sub-domain IIA in the protein structure.
authors.affiliation: Centre for Advanced Studies, Department of Chemistry, North-Eastern Hill University, Shillong 793 022, India.
authors.forename: Mullah Muhaiminul
authors.initials: MM
authors.lastname: Islam
authors.affiliation: Centre for Advanced Studies, Department of Chemistry, North-Eastern Hill University, Shillong 793 022, India.
authors.forename: Vikash K
authors.initials: VK
authors.lastname: Sonu
authors.affiliation: Centre for Advanced Studies, Department of Chemistry, North-Eastern Hill University, Shillong 793 022, India.
authors.forename: Pynsakhiat Miki
authors.initials: PM
authors.lastname: Gashnga
authors.affiliation: Centre for Advanced Studies, Department of Chemistry, North-Eastern Hill University, Shillong 793 022, India.
authors.forename: N Shaemningwar
authors.initials: NS
authors.lastname: Moyon
authors.affiliation: Centre for Advanced Studies, Department of Chemistry, North-Eastern Hill University, Shillong 793 022, India. Electronic address: smitra@nehu.ac.in.
authors.forename: Sivaprasad
authors.initials: S
authors.lastname: Mitra
mesh_terms: D000890:Anti-Infective Agents / Q000378:metabolism*; D001665:Binding Sites; D002110:Caffeine / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000378:metabolism*; D005453:Fluorescence; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D055672:Static Electricity; D013411:Sulfadiazine / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D000890:Anti-Infective Agents; D000697:Central Nervous System Stimulants; D012709:Serum Albumin; D013411:Sulfadiazine; D002110:Caffeine
keywords: Caffeine; Fluorescence quenching; Human serum albumin; Hydrophobic & electrostatic interaction; Molecular docking; Sulfadiazine