Synthesis, Characterization and Biological Evaluation of New 3,5-Disubstituted-Pyrazoline Derivatives as Potential Anti-Mycobacterium tuberculosis H37Ra Compounds

Autor: Mohammad Tasyriq Che Omar, Mohamad Nurul Azmi, Thaigarajan Parumasivam, Hasnah Osman, Kok Tong Wong, Unang Supratman
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Protein Conformation
Pharmaceutical Science
01 natural sciences
Analytical Chemistry
Sterol 14-Demethylase
chemistry.chemical_compound
Catalytic Domain
Drug Discovery
Fluconazole
0303 health sciences
Semicarbazide
biology
Semicarbazides
Molecular Docking Simulation
14-alpha Demethylase Inhibitors
Chemistry (miscellaneous)
Thermodynamics
Molecular Medicine
alpha-sterol demethylase
Heteronuclear single quantum coherence spectroscopy
Protein Binding
Chalcone
pyrazolines
Stereochemistry
Microbial Sensitivity Tests
Article
lcsh:QD241-441
Mycobacterium tuberculosis
03 medical and health sciences
Minimum inhibitory concentration
Bacterial Proteins
lcsh:Organic chemistry
Isoniazid
Protein Interaction Domains and Motifs
Physical and Theoretical Chemistry
030304 developmental biology
Minimum bactericidal concentration
010405 organic chemistry
Organic Chemistry
molecular docking
biology.organism_classification
In vitro
0104 chemical sciences
chemistry
Structural Homology
Protein
biology.protein
Pyrazoles
Demethylase
antitubercular agents
Zdroj: Molecules
Molecules, Vol 26, Iss 2081, p 2081 (2021)
Volume 26
Issue 7
ISSN: 1420-3049
Popis: A total of fourteen pyrazoline derivatives were synthesized through cyclo-condensation reactions by chalcone derivatives with different types of semicarbazide. These compounds were characterized by IR, 1D-NMR (1H, 13C and Distortionless Enhancement by Polarization Transfer - DEPT-135) and 2D-NMR (COSY, HSQC and HMBC) as well as mass spectroscopy analysis (HRMS). The synthesized compounds were tested for their antituberculosis activity against Mycobacterium tuberculosis H37Ra in vitro. Based on this activity, compound 4a showed the most potent inhibitory activity, with a minimum inhibitory concentration (MIC) value of 17 μM. In addition, six other synthesized compounds, 5a and 5c–5g, exhibited moderate activity, with MIC ranges between 60 μM to 140 μM. Compound 4a showed good bactericidal activity with a minimum bactericidal concentration (MBC) value of 34 μM against Mycobacterium tuberculosis H37Ra. Molecular docking studies for compound 4a on alpha-sterol demethylase was done to understand and explore ligand–receptor interactions, and to hypothesize potential refinements for the compound.
Databáze: OpenAIRE
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