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A novel sulfamethoxazole derivative as an inhibitory agent against HSP70: A combination of computational with in vitro studies
- Source :
- International Journal of Biological Macromolecules. 189:194-205
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- In the current study, a novel derivative of sulfamethoxazole (a sulfonamide containing anti-biotic) named ZM-093 (IUPAC name: (E)-4-((4-(bis(2-hydroxyethyl)amino)phenyl)diazenyl)-N-(5-methylisoxazole-3-yl)benzenesulfonamide) was synthesized via common diazotization-coupling reactions from sulfamethoxazole and subsequently characterized through NMR/FT-IR spectroscopy. After evaluation, the compound was geometrically optimized at the DFT level of theory with BL3YP method and 6/31++G (d,p) basis set and from the optimized structure, several molecular descriptors important in the biological reactivity of the compound, such as global reactivity parameters, molecular electrostatic potential, average local ionization energy, and drug-likeness features of the compound were computationally analyzed. The experimental in vitro investigations of the interaction between ZM-093 and heat shock protein 70 (HSP70), a protein that is highly expressed in several types of cancers, exhibited a significant inhibitory effect against the chaperone activity of HSP70 for the titled compound (P-value < 0.01) and the comparison between the experimental studies with the mentioned computational analysis, as well as molecular docking, illustrated that ZM-093 may inhibit HSP70 through binding to its substrate-binding domain. Finally, by taking all the previous results into account, a new method for assessing the inhibitory activity of ligand to HSP70 is introduced based on protonography, a recently developed method that is dependent on the catalytic activity of carbonic anhydrase on polyacrylamide gel electrophoresis.
- Subjects :
- Protein Denaturation
Magnetic Resonance Spectroscopy
Sulfamethoxazole
Stereochemistry
Molecular Conformation
Biochemistry
Protein Refolding
chemistry.chemical_compound
Structural Biology
Molecular descriptor
Carbonic anhydrase
Computer Simulation
HSP70 Heat-Shock Proteins
Reactivity (chemistry)
Molecular Biology
Polyacrylamide gel electrophoresis
Carbonic Anhydrases
Adenosine Triphosphatases
chemistry.chemical_classification
biology
General Medicine
Ligand (biochemistry)
In vitro
Sulfonamide
Molecular Docking Simulation
Pharmaceutical Preparations
chemistry
biology.protein
Colorimetry
Protons
Derivative (chemistry)
Subjects
Details
- ISSN :
- 01418130
- Volume :
- 189
- Database :
- OpenAIRE
- Journal :
- International Journal of Biological Macromolecules
- Accession number :
- edsair.doi.dedup.....22c32a78877f5622a7c5c9501cdc5140
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2021.08.128