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Biological Evaluation and Molecular Docking with In Silico Physicochemical, Pharmacokinetic and Toxicity Prediction of Pyrazolo[1,5- a ]pyrimidines.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2020 Mar 21; Vol. 25 (6). Date of Electronic Publication: 2020 Mar 21. - Publication Year :
- 2020
-
Abstract
- Pyrazolo[1,5- a ]pyrimidines 5a - c , 9a - c and 13a - i were synthesized for evaluation of their in vitro antimicrobial properties against some microorganisms and their immunomodulatory activity. The biological activities of pyrazolo[1,5- a ]pyrimidines showed that the pyrazolo[1,5- a ]pyrimidines ( 5c , 9a , 9c , 13a , 13c , 13d , 13e and 13h ) displayed promising antimicrobial and immunomodulatory activities. Studying the in silico predicted physicochemical, pharmacokinetic, ADMET and drug-likeness properties for the pyrazolo[1,5- a ]pyrimidines 5a - c , 9a - c and 13a - i confirmed that most of the compounds (i) were within the range set by Lipinski's rule of five, (ii) show higher gastrointestinal absorption and inhibition of some CYP isoforms, and (iii) have a carcinogenicity test that was predicted as negative and hERG test that presented medium risk. Moreover, the molecular docking study demonstrated that the compounds 5c , 9a , 9c , 13a , 13c , 13d , 13e and 13h are potent inhibitors of 14-alpha demethylase, transpeptidase and alkaline phosphatase enzymes. This study could be valuable in the discovery of a new series of drugs.
- Subjects :
- 14-alpha Demethylase Inhibitors pharmacology
Alkaline Phosphatase antagonists & inhibitors
Aspergillus drug effects
Caco-2 Cells
Candida albicans drug effects
Carcinogenicity Tests adverse effects
Computer Simulation
Drug Design
Enterococcus faecalis drug effects
Escherichia coli drug effects
Fusarium drug effects
Humans
Molecular Docking Simulation
Molecular Structure
Peptidyl Transferases antagonists & inhibitors
Pseudomonas aeruginosa drug effects
Pyrazoles chemistry
Pyrazoles pharmacokinetics
Pyrazoles toxicity
Pyrimidines chemistry
Pyrimidines pharmacokinetics
Pyrimidines toxicity
Salmonella typhi drug effects
Staphylococcus aureus drug effects
Structure-Activity Relationship
Anti-Bacterial Agents pharmacology
Anti-Infective Agents pharmacology
Fungi drug effects
Gram-Negative Bacteria drug effects
Gram-Positive Bacteria drug effects
Pyrazoles pharmacology
Pyrimidines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 25
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 32245177
- Full Text :
- https://doi.org/10.3390/molecules25061431