Unknown

Dataset Information

0

Development of a Novel Class of Pyridazinone Derivatives as Selective MAO-B Inhibitors.

ABSTRACT: Sixteen compounds (TR1-TR16) were synthesized and evaluated for their inhibitory activities against monoamine oxidase A and B (MAOs). Most of the derivatives showed potent and highly selective MAO-B inhibition. Compound TR16 was the most potent inhibitor against MAO-B with an IC50 value of 0.17 μM, followed by TR2 (IC50 = 0.27 μM). TR2 and TR16 selectivity index (SI) values for MAO-B versus MAO-A were 84.96 and higher than 235.29, respectively. Compared to the basic structures, the para-chloro substituent in TR2 and TR16 increased the inhibitory activity of MAO-B. TR2 and TR16 were reversible MAO-B inhibitors that were competitive, with Ki values of 0.230 ± 0.004 and 0.149 ± 0.016 µM, respectively. The PAMPA method indicated that compounds TR2 and TR16 had the tendency to traverse the blood-brain barrier. Docking investigations revealed that lead compounds were beneficial for MAO-B inhibition via association with key as well as selective E84 or Y326 residues, but not for MAO-A inhibition via interaction primarily driven by hydrophobic contacts. In conclusion, TR2 and TR16 are therapeutic prospects for the management of multiple neurodegenerative diseases.

SUBMITTER: Alagoz MA 

PROVIDER: S-EPMC9230784 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Development of a Novel Class of Pyridazinone Derivatives as Selective MAO-B Inhibitors.

Alagöz Mehmet Abdullah MA   Oh Jong Min JM   Zenni Yaren Nur YN   Özdemir Zeynep Z   Abdelgawad Mohamed A MA   Naguib Ibrahim A IA   Ghoneim Mohammed M MM   Gambacorta Nicola N   Nicolotti Orazio O   Kim Hoon H   Mathew Bijo B  

Molecules (Basel, Switzerland) 20220613 12

Sixteen compounds (<b>TR1-TR16</b>) were synthesized and evaluated for their inhibitory activities against monoamine oxidase A and B (MAOs). Most of the derivatives showed potent and highly selective MAO-B inhibition. Compound <b>TR16</b> was the most potent inhibitor against MAO-B with an IC<sub>50</sub> value of 0.17 μM, followed by <b>TR2</b> (IC<sub>50</sub> = 0.27 μM). <b>TR2</b> and <b>TR16</b> selectivity index (SI) values for MAO-B versus MAO-A were 84.96 and higher than 235.29, respecti  ...[more]

Similar Datasets

Unknown Novel 1-(2-pyrimidin-2-yl)piperazine derivatives as selective monoamine oxidase (MAO)-A inhibitors.
| S-EPMC6009961 | biostudies-literature
Unknown Discovery of Novel Pyrido-pyridazinone Derivatives as FER Tyrosine Kinase Inhibitors with Antitumor Activity.
| S-EPMC6511961 | biostudies-literature
Unknown Development of Isopropyl-Tailed Chalcones as a New Class of Selective MAO-B Inhibitors for the Treatment of Parkinson's Disorder.
| S-EPMC9947953 | biostudies-literature
Unknown Computationally Assisted Lead Optimization of Novel Potent and Selective MAO-B Inhibitors.
| S-EPMC8533211 | biostudies-literature
Unknown Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors.
| S-EPMC8587871 | biostudies-literature
Unknown Novel Disulfiram Derivatives as ALDH1a1-Selective Inhibitors.
| S-EPMC8778300 | biostudies-literature
Unknown Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors.
| S-EPMC7571065 | biostudies-literature
Unknown Design, Synthesis and Comprehensive Investigations of Pyrrolo[3,4-d]pyridazinone-Based 1,3,4-Oxadiazole as New Class of Selective COX-2 Inhibitors.
| S-EPMC7766220 | biostudies-literature
Unknown New class of thio/semicarbazide-based benzyloxy derivatives as selective class of monoamine oxidase-B inhibitors.
| S-EPMC11682371 | biostudies-literature
Unknown Design, Synthesis and Biological Evaluation of Novel N-Pyridyl-Hydrazone Derivatives as Potential Monoamine Oxidase (MAO) Inhibitors.
| S-EPMC6017090 | biostudies-literature