Designing a natural inhibitor against human kynurenine aminotransferase type II and a comparison with PF-04859989: a computational effort against schizophrenia

Noorbakhsh, Akbar; Koushki, Elnaz Hosseininezhadian; Farshadfar, Chiako; Ardalan, Noeman

doi:10.1080/07391102.2021.1893817

Cited by 9 publications

(3 citation statements)

References 64 publications

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“…Over the last decade, there has been a rapid increase in CADD-based studies of depression, including docking studies of ligands for serotonin reuptake [171,172], MAO A and MAO B [173,174], dual action on MAO-B/AChE [175], glycogen synthase kinase [176], sodium hNaV1.2 or hNaV1.7 channels [177], serotonin receptors (5HT1A, 5-HT2A, 5-HT2C and 5-HT4) [171,[178][179][180][181], adenosine A1/A2A receptors [182], T-type calcium channels [183], tryptophan 2,3-dioxygenase [184] and sigma receptor [185]. Similarly, application of docking in psychoses involved ligands for serotonin 5HT2 and dopamine D2 receptors [186], α4β2 and α7 nicotinic acetylcholine receptors [187,188], phosphodiesterase 10A [189], MAO A and B [190], a syntaxin-binding protein (STXBP1) [191], NMDA type subunit 1 (GRIN1) [192], fatty acid binding protein 7 (FABP7) [193,194], metabotropic glutamate mGluR5 receptor [195], ionotropic GABA-A receptor [196], glycine transporter type 1 (GlyT1) [197] and kynurenine aminotransferase II (KATII) [198].…”

Section: In Silico-driven Search For Novel Therapeutic Agentsmentioning

confidence: 99%

Towards Novel Potential Molecular Targets for Antidepressant and Antipsychotic Pharmacotherapies

Kositsyn

Abreu

Колесникова

et al. 2023

IJMS

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Depression and schizophrenia are two highly prevalent and severely debilitating neuropsychiatric disorders. Both conventional antidepressant and antipsychotic pharmacotherapies are often inefficient clinically, causing multiple side effects and serious patient compliance problems. Collectively, this calls for the development of novel drug targets for treating depressed and schizophrenic patients. Here, we discuss recent translational advances, research tools and approaches, aiming to facilitate innovative drug discovery in this field. Providing a comprehensive overview of current antidepressants and antipsychotic drugs, we also outline potential novel molecular targets for treating depression and schizophrenia. We also critically evaluate multiple translational challenges and summarize various open questions, in order to foster further integrative cross-discipline research into antidepressant and antipsychotic drug development.

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Section: In Silico-driven Search For Novel Therapeutic Agentsmentioning

confidence: 99%

Towards Novel Potential Molecular Targets for Antidepressant and Antipsychotic Pharmacotherapies

Kositsyn

Abreu

Колесникова

et al. 2023

IJMS

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“…Where the free energy of a state (L denotes ligand and P represents protein) was computed through processing ligand-receptor conformations (36)(37)(38)(39)(40).…”

Section: Binding Free Energymentioning

confidence: 99%

Discovery of a Potent Inhibitor to Overcome Carbapenem Resistance in Pseudomonas aeruginosa Strains via Inhibition of VIM-2 Metallo-β-lactamases

Moosavi

Madani

Mirzaie

et al. 2022

J Health Rep Technol

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Background: Mutations in bacteria frequently occur that display a crucial need for new antimicrobial agents. Metallo-β-lactamases (MBLs) are a growing threat to maintaining the effectiveness of beta-lactam antibiotics. Resistance to beta-lactam antibiotics is one of the most common types of antibiotic resistance, which causes the ineffectiveness of antibiotics. Objectives: This study aimed to identify a novel inhibitor using molecular dynamics simulations to inhibit VIM-2 Metallo-β-lactamases and overcome carbapenem resistance in Pseudomonas aeruginosa strains. Methods: Computational biology tools were employed for this study, including molecular dynamics, binding free energy, virtual screening, and docking. Natural compounds were taken from the ZINC databank and prepared. At the next stage, the prepared compounds were screened based on docking energy in the active site of VIM-2 MBL by Schrödinger (Maestro) software, and better compounds were selected. Captopril was chosen as a positive control inhibitor for VIM-2 MBLs. Ultimately, molecular dynamics simulations were performed using GROMACS software, and outputs were analyzed. Results: Maestro software's screening results showed that ZINC00517765 was the best inhibitor with -12.29 kcal mol-1 docking energy. The ADME investigations revealed that ZINC00517765 had an appropriate range of pharmacokinetics, lipophilicity, and drug-likeness features as an inhibitor of VIM-2 MBL. Molecular dynamics outcomes explicated that VIM-2 MBL in the presence of ZINC00517765 had better stability during simulation. The results of the MM-PBSA study illustrated that ZINC00517765 with -72.29 kJ mol-1 binding free energy was more potent than Captopril with -23.39 kJ mol-1. Conclusions: This study showed that VIM-2 MBL in the presence of ZINC00517765 has suitable stability during simulation. Also, more hydrogen bonds and stronger binding free energy than Captopril confirm that ZINC00517765 is a proper candidate for further studies and laboratory investigation.

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“…As part of this pathway, the enzyme kynurenine-3-monooxygenase (KMO) converts kynurenine (KYN) to 3-hydroxykynurenine (3HK), a free radical generator that causes neuronal cell death and overstimulation of glutamate receptors [ 3 , 5 ]. Compounds that decrease the levels of 3HK, especially KMO inhibitors such as UPF-648 (IC50 = 20 nM), KNS366, and GSK 366 (IC50 = 2.3 nM), are being considered for treating several diseases [ 3 , [5] , [6] , [7] , [8] , [9] , [10] , [11] ].…”

Section: Introductionmentioning

confidence: 99%

Identification of potent inhibitors of kynurenine-3-monooxygenase from natural products: In silico and in vitro approaches

Rebai,

Carmena-Bargueño,

Toumi

et al. 2024

Heliyon

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Designing a natural inhibitor against human kynurenine aminotransferase type II and a comparison with PF-04859989: a computational effort against schizophrenia

Cited by 9 publications

References 64 publications

Towards Novel Potential Molecular Targets for Antidepressant and Antipsychotic Pharmacotherapies

Towards Novel Potential Molecular Targets for Antidepressant and Antipsychotic Pharmacotherapies

Discovery of a Potent Inhibitor to Overcome Carbapenem Resistance in Pseudomonas aeruginosa Strains via Inhibition of VIM-2 Metallo-β-lactamases

Identification of potent inhibitors of kynurenine-3-monooxygenase from natural products: In silico and in vitro approaches

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