A novel series of imidazole linked thiazolidinone hybrid molecules were designed and synthesized through a feasible three step reaction protocol. The synthesized molecules were characterized by FT-IR, 1H NMR, 13C NMR and HRMS techniques. In vitro susceptibility tests against some gram positive (Staphylococcus aureus, Bacillus subtilis) and gram negative bacteria (Escherichia coli and Pseudomonas aeruginosa) showed broad spectrum potency of the molecules. The most active molecule (S2A7) gave MIC value of 2.0 µg/mL which is at par with the reference drug Streptomycin. Structure activity relationships revealed nitro and chloro groups are crucial for bioactivity if present at meta position of arylidene ring in 3-(3-(imidazol-1-yl)propyl)-5-(benzylidene)-2-(phenylimino)thiazolidin-4-one. DNA and BSA binding studies of S2A7 under simulated physiological pH were probed with UV-Vis., fluorescence quenching, gel electrophoresis and molecular docking techniques. These studies established that S2A7 has strong affinity towards DNA and binds at the minor groove of DNA with binding constant (Kb) of 0.1287 x 102 L mol-1. Molecular docking simulations predicted binding affinity of -9.2 & -7.2 kcal/mol respectively with DNA & BSA. Van der Waals forces and hydrogen bonding interactions were predicted as the main forces of interaction. In case of DNA S2A7 exhibited specific affinity towards adenine-thiamine base pairs. The compound forms a stable complex with BSA by binding at subdomain IIIA indicating high biodistribution.
Rationale design and synthesis of some novel imidazole linked thiazolidinone hybrid molecules as DNA minor groove binders
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