title: Structural characterization of new Schiff bases of sulfamethoxazole and sulfathiazole, their antibacterial activity and docking computation with DHPS protein structure.
abstract: New Schiff bases (1, 2) of substituted salicylaldehydes and sulfamethoxazole (SMX)/sulfathiazole (STZ) are synthesized and characterized by elemental analysis and spectroscopic data. Single crystal X-ray structure of one of the compounds (E)-4-((3,5-dichloro-2-hydroxybenzylidene)amino)-N-(5-methylisoxazol-3-yl)benzenesulfonamide (1c) has been determined. Antimicrobial activities of the Schiff bases and parent sulfonamides (SMX, STZ) have been examined against several Gram-positive and Gram-negative bacteria and sulfonamide resistant pathogens; the lowest MIC is observed for (E)-4-((3,5-dichloro-2-hydroxybenzylidene)amino)-N-(thiazol-2-yl)benzene sulfonamide (2c) (8.0 μg mL(-1)) and (E)-4-((3,5-dichloro-2-hydroxybenzylidene)amino)-N-(5-methylisoxazol-3-yl)benzene sulfonamide (1c) (16.0 μg mL(-1)) against sulfonamide resistant pathogens. DFT optimized structures of the Schiff bases have been used to carry out molecular docking studies with DHPS (dihydropteroate synthase) protein structure (downloaded from Protein Data Bank) using Discovery Studio 3.5 to find the most preferred binding mode of the ligand inside the protein cavity. The theoretical data have been well correlated with the experimental results. Cell viability assay and ADMET studies predict that 1c and 2c have good drug like characters.
authors.affiliation: Department of Chemistry, Jadavpur University, Kolkata 700 032, India.
authors.forename: Sudipa
authors.initials: S
authors.lastname: Mondal
authors.affiliation: Central Research Facility, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
authors.forename: Santi M
authors.initials: SM
authors.lastname: Mandal
authors.affiliation: Department of Chemistry, Jadavpur University, Kolkata 700 032, India.
authors.forename: Tapan Kumar
authors.initials: TK
authors.lastname: Mondal
authors.affiliation: Department of Chemistry, Jadavpur University, Kolkata 700 032, India. Electronic address: c_r_sinha@yahoo.com.
authors.forename: Chittaranjan
authors.initials: C
authors.lastname: Sinha
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004094:Dihydropteroate Synthase / Q000737:chemistry* / Q000378:metabolism; D016972:Enterobacter cloacae; D004926:Escherichia coli; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D011485:Protein Binding; D012545:Schiff Bases / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D013211:Staphylococcus aureus; D013420:Sulfamethoxazole / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D000077589:Sulfathiazole; D013432:Sulfathiazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D012545:Schiff Bases; D013432:Sulfathiazoles; D004094:Dihydropteroate Synthase; D013420:Sulfamethoxazole; D000077589:Sulfathiazole
keywords: Antibacterial activity; DFT computation; Molecular docking study; Spectra and structure; Sulfonamide Schiff bases