title: Synthesis and DNA-binding study of imidazole linked thiazolidinone derivatives.
abstract: A novel series of imidazole-linked thiazolidinone hybrid molecules were designed and synthesized through a feasible synthetic protocol. The molecules were characterized with Fourier transform infrared (FT-IR),1H nuclear magnetic resonance (NMR),13C NMR and high-resolution mass spectrometry (HRMS) techniques. In vitro susceptibility tests against Gram-positive (S. aureus and B. subtilis) and Gram-negative bacteria (E. coli and P. aeruginosa) gave highly promising results. The most active molecule (3e) gave a minimal inhibitory concentration (MIC) value of 3.125 μg/mL which is on par with the reference drug streptomycin. Structure-activity relationships revealed activity enhancement by nitro and chloro groups when they occupied meta position of the arylidene ring in 2-((3-(imidazol-1-yl)propyl)amino)-5-benzylidenethiazolidin-4-ones. DNA-binding study of the most potent molecule 3e with salmon milt DNA (sm-DNA) under simulated physiological pH was probed with UV-visible absorption, fluorescence quenching, gel electrophoresis and molecular docking techniques. These studies established that compound 3e has a strong affinity towards DNA and binds at DNA minor groove with a binding constant (Kb) 0.18 × 102L mol-1. Molecular docking simulations predicted strong affinity of 3e towards DNA with a binding affinity (ΔG) -8.5 kcal/mol. Van der Waals forces, hydrogen bonding and hydrophobic interactions were predicted as the main forces of interaction. The molecule 3e exhibited specific affinity towards adenine-thiamine base pairs. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Synthetic Organic Chemistry and Molecular Modelling Laboratory, Department of Chemistry, Dr. Hari Singh Gour University, Sagar, M.P, 470003, India.
authors.forename: Javeed Ahmad
authors.initials: JA
authors.lastname: War
authors.affiliation: Synthetic Organic Chemistry and Molecular Modelling Laboratory, Department of Chemistry, Dr. Hari Singh Gour University, Sagar, M.P, 470003, India.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Srivastava
authors.affiliation: Synthetic Organic Chemistry and Molecular Modelling Laboratory, Department of Chemistry, Dr. Hari Singh Gour University, Sagar, M.P, 470003, India.
authors.forename: Savitri Devi
authors.initials: SD
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D007093:Imidazoles / Q000737:chemistry*; D008297:Male; D008826:Microbial Sensitivity Tests; D012474:Salmon; D013094:Spermatozoa / Q000737:chemistry; D013329:Structure-Activity Relationship; D053778:Thiazolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D007093:Imidazoles; D053778:Thiazolidines; D004247:DNA
keywords: 2-((3-(imidazol-1-yl)propyl)amine); DNA binding; antimicrobial activity; molecular docking