Design, synthesis and DNA-binding study of some novel morpholine linked thiazolidinone derivatives.
The emergence of multiple drug resistance amongst bacterial strains resulted in many clinical drugs to be ineffective. Being vulnerable to bacterial infections any lack in the development of new antimicrobial drugs could pose a serious threat to public health. Here we report design and synthesis of a novel class of morpholine linked thiazolidinone hybrid molecules. The compounds were characterized by FT-IR, NMR and HRMS techniques. Susceptibility tests showed that most of the synthesized molecules were highly active against multiple bacterial strains. Compound 3f displayed MIC values which were better than the standard drug for most of the tested strains. DNA being a well defined target for many antimicrobial drugs was probed as possible target for these synthetic molecules. DNA-binding study of 3f with sm-DNA was probed through UV-vis absorption, fluorescence quenching, gel electrophoresis and molecular docking techniques. The studies revealed that compound 3f has strong affinity towards DNA and binds at the minor groove. The docking studies revealed that the compound 3f shows preferential binding towards A/T residues.
Synthetic Organic Chemistry & Molecular Modelling Laboratory, Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar, MP 470003, India.
Javeed Ahmad
JA
War
Synthetic Organic Chemistry & Molecular Modelling Laboratory, Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar, MP 470003, India. Electronic address: profskssgr@gmail.com.
Santosh Kumar
SK
Srivastava
Synthetic Organic Chemistry & Molecular Modelling Laboratory, Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar, MP 470003, India.
Savitri Devi
SD
Srivastava
D000890:Anti-Infective Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D060326:Chemistry Techniques, Synthetic; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013844:Thiazoles / Q000737:chemistry
D000890:Anti-Infective Agents; D009025:Morpholines; D013844:Thiazoles; D004247:DNA
4-(2-Aminoethyl)morpholine; Broad spectrum antimicrobials; DNA-binding; Molecular docking