Design, Synthesis, Docking Studies and Monoamine Oxidase Inhibition of a Small Library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazoles

被引:25
作者
Guglielmi, Paolo [1 ]
Carradori, Simone [2 ]
Poli, Giulio [3 ]
Secci, Daniela [1 ]
Cirilli, Roberto [4 ]
Rotondi, Giulia [1 ]
Chimenti, Paola [1 ]
Petzer, Anel [5 ,6 ]
Petzer, Jacobus P. [5 ,6 ]
机构
[1] Sapienza Univ Rome, Dipartimento Chim & Tecnol Farmaco, Ple A Moro 5, I-00185 Rome, Italy
[2] GD Annunzio Univ Chieti Pescara, Dept Pharm, Via Vestini 31, I-66100 Chieti, Italy
[3] Univ Pisa, Dept Pharm, Via Bonanno 6, I-56126 Pisa, Italy
[4] Ist Super Sanita, Ctr Nazl Controllo & Valutaz Farm, Viale Regina Elena 299, I-00161 Rome, Italy
[5] North West Univ, Sch Pharm, Pharmaceut Chem, ZA-2520 Potchefstroom, South Africa
[6] North West Univ, Ctr Excellence Pharmaceut Sci, ZA-2520 Potchefstroom, South Africa
关键词
pyrazoline; monoamine oxidase; enantioseparation; molecular modelling; prenyl; FASCINATING MOLECULAR FRAMEWORK; ENANTIOSEPARATION ABILITY; MAO INHIBITORS; DERIVATIVES; 3-(PHENYL-4-OXY)-5-PHENYL-4,5-DIHYDRO-(1H)-PYRAZOLE;
D O I
10.3390/molecules24030484
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
New N-acetyl/N-thiocarbamoylpyrazoline derivatives were designed and synthesized in high yields to assess their inhibitory activity and selectivity against human monoamine oxidase A and B. The most important chiral compounds were separated into their single enantiomers and tested. The impact of the substituents at N1, C3 and C5 positions as well the influence of the configuration of the C5 on the biological activity were analyzed. Bulky aromatic groups at C5 were not tolerated. p-Prenyloxyaryl moiety at C3 oriented the selectivity toward the B isoform. The results were also corroborated by molecular modelling studies providing new suggestions for the synthesis of privileged structures to serve as lead compounds for the treatment of mood disorders and neurodegenerative diseases.
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页数:21
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