Review
Chemistry, Medicinal
Ashwani Kumar, Meenakshi Bhatia, Archana Kapoor, Parvin Kumar, Sunil Kumar, Sunil Kumar
Summary: Monoamine oxidase enzyme plays an essential role in brain function regulation, with its inhibitors showing potential in the treatment of neurological disorders. Reversible MAO inhibitors, which have been recently studied, may serve as safer alternatives to old monoamine oxidase inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Edward E. Putnins, Verena Goebeler, Mahyar Ostadkarampour
Summary: RG0216 significantly decreased LPS-induced IL-6 and IL-1 beta gene and protein expression in an epithelial cell culture model, with similar effectiveness to deprenyl. This reduction occurred downstream of the cAMP-PKA/EPAC signaling cascade, providing a novel mechanism by which MAO-B selective inhibitors regulate LPS-induced cytokine expression.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Nutrition & Dietetics
Zhen Tian, Xinyue Wang, Tianshu Han, Maoqing Wang, Hua Ning, Changhao Sun
Summary: In this study, the activation of MAOB under pathological conditions was found to be a novel source of cardiovascular ROS. This ROS-induced endothelial dysfunction contributes to chronic vascular inflammation and atherosclerosis. The study also revealed the role of MAOB inhibitor in reducing oxidative stress and improving endothelial function through modulating gut microbiota.
Article
Chemistry, Analytical
Xiaoya Wang, Xiaolei Song, Peng Li, Shihao Sun, Jian Mao, Songqin Liu, Wei Wei
Summary: This study reports a simple fluorescence assay for detecting MAO-B using the cage function of glyoxal and phenethylamine on G-rich DNA. The method involves the destruction of G-quadruplex structure, leading to reduced fluorescence intensity, and an increase in G-quadruplex structure due to oxidation of phenethylamine. The assay has a wide linear range and low detection limit, making it suitable for early diagnosis of neurodegenerative diseases.
SENSORS AND ACTUATORS B-CHEMICAL
(2022)
Article
Biochemistry & Molecular Biology
Jacqueline Heger, Tamara Szabados, Paulin Brosinsky, Peter Bencsik, Peter Ferdinandy, Rainer Schulz
Summary: The knockout of monoamine oxidase (MAO)-B specifically in cardiomyocytes reduces myocardial ischemia/reperfusion (I/R) injury in vitro. In this study, the researchers investigated the impact of MAO-B knockout on myocardial infarction (MI) following I/R in male and female mice. They found that MAO-B knockout protected male mice against MI, but had no effect on infarct size in female mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Narayan D. Chaurasiya, Francisco Leon, Ilias Muhammad, Babu L. Tekwani
Summary: Monoamine oxidase inhibitors (MAOIs) are important drugs for treating depression and neurological disorders, with natural product MAOIs showing potential as safer alternatives. Traditional plants and herbal formulations containing MAOI constituents have psychoactive and neuroprotective effects, indicating therapeutic potential for neuroblastoma treatment.
Article
Biochemistry & Molecular Biology
Amina Moutayakine, Carolina Marques, Oscar Lopez, Donatella Bagetta, Luisa Leitzbach, Stefanie Hagenow, Elisabete P. Carreiro, Holger Stark, Stefano Alcaro, Jose G. Fernandez-Bolanos, Anthony J. Burke
Summary: A new gem-dimethylchroman-4-ol family of compounds was developed in this study, showing good inhibition of equine serum butyrylcholinesterase (eqBuChE), making them suitable as inhibitors for BuChE.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Vedanjali Gogineni, Manal A. Nael, Narayan D. Chaurasiya, Khaled M. Elokely, Christopher R. McCurdy, John M. Rimoldi, Stephen J. Cutler, Babu L. Tekwani, Francisco Leon
Summary: A series of dietary flavonoid acacetin 7-O-methyl ether derivatives were computationally designed to improve selectivity and potency against monoamine oxidase (MAO) B. Compounds 1c, 2c, 3c, and 4c showed potent inhibition against MAO-B with over a thousand-fold selectivity compared to MAO-A. Compounds 1c and 2c also displayed reversible inhibition of MAO-B, suggesting potential therapeutic applications for Parkinson's Disease and other neurological disorders.
Article
Biochemistry & Molecular Biology
Liliana Pacureanu, Alina Bora, Luminita Crisan
Summary: In order to discover new MAO-B inhibitors, we developed a comprehensive computational approach including a pharmacophoric atom-based 3D QSAR model, activity cliffs analysis, fingerprint analysis, and molecular docking analysis. The AAHR.2 hypothesis provided a statistically significant 3D QSAR model, and hydrophobic and electron-withdrawing fields revealed the relationship between structural characteristics and inhibitory activity. The quinolin-2-one scaffold played a key role in selectivity towards MAO-B. Molecular docking analysis confirmed the interactions with crucial residues responsible for MAO-B activity. The computational scenario presented here will assist chemists in designing and predicting new potent and selective MAO-B inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ahmed Elkamhawy, Hyeon Jeong Kim, Mohamed H. Elsherbeny, Sora Paik, Jong-Hyun Park, Lizaveta Gotina, Magda H. Abdellattif, Noha A. Gouda, Jungsook Cho, Kyeong Lee, Ae Nim Pae, Ki Duk Park, Eun Joo Roh
Summary: This study reported the design and synthesis of twenty-six new indole derivatives as potential MAO-B inhibitors, with compound 5 showing high inhibitory activity against hMAO-B and good selectivity index. The compound also demonstrated low cytotoxicity, promising neuroprotective effect, and high CNS bioavailability, making it a potent candidate for PD treatment.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Muhammad Shahid Nadeem, Jalaluddin Azam Khan, Umer Rashid
Summary: The study focuses on synthesizing multi-target compounds that can inhibit both cholinesterases and monoamine oxidase. A series of fluoxetine and sertraline hybrids showed excellent inhibition activity, with compounds 17 and 22 potentially blocking neurodegenerative effects in mice.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Alja Prah, Tanja Gavranic, Andrej Perdih, Marija Sollner Dolenc, Janez Mavri
Summary: In this study, we conducted computational and dynamic analysis to investigate the binding between a series of substituted beta-carboline natural products and MAO-A enzyme. The results provide important insights for rational structure-based drug design and optimization, particularly in the treatment of mental disorders such as depression.
Article
Radiology, Nuclear Medicine & Medical Imaging
Kenji Ishibashi, Yoshiharu Miura, Tetsuro Tago, Jun Toyohara, Mana Higashihara, Atsushi Iwata, Kenji Ishii
Summary: This study examined the distribution pattern of F-18-THK5351 in the healthy brain and found that its uptake largely reflects the concentrations of MAO-B under normal conditions.
CLINICAL NUCLEAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Magdalena Kondeva-Burdina, Javor Mitkov, Iva Valkova, Lily Peikova, Maya Georgieva, Alexander Zlatkov
Summary: The neurotoxic, neuroprotective, and MAO-B inhibitory effects of a series of N'-substituted 3-(1,3,7-trimethyl-xanthin-8-ylthio)propanehydrazides were evaluated. Compounds N'-(2,3-dimethoxybenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6k) and N'-(2-hydroxybenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6l) were identified as the most promising. QSTR analysis revealed that reduced lipophilicity and smaller dipole moments of the molecules contribute to lower neurotoxicity. These findings provide initial information for the further design of (xanthinyl-8-ylthio)propanhydrazides with potential hMAOB inhibitory effect and pronounced neuroprotection.
Article
Biochemistry & Molecular Biology
Damijan Knez, Martina Hrast, Rok Frlan, Anja Pislar, Simon Zakelj, Janko Kos, Stanislav Gobec
Summary: The therapeutic indications for monoamine oxidases A and B (MAO-A and MAO-B) inhibitors have led to the discovery of reversible MAO inhibitors based on biological studies. Two hit compounds were identified as MAO-B inhibitors from screening of a compound library, and derived two series of inhibitors. These selective MAO-B inhibitors showed favorable blood-brain barrier permeation and low cytotoxicity.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Luca Giacinto Iacovino, Simone Savino, Annika J. E. Borg, Claudia Binda, Bernd Nidetzky, Andrea Mattevi
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Editorial Material
Biochemistry & Molecular Biology
Filippo Fiorentini, Callum R. Nicoll, Andrea Mattevi
Article
Chemistry, Medicinal
Luca G. Iacovino, Luca Pinzi, Giorgio Facchetti, Beatrice Bortolini, Michael S. Christodoulou, Claudia Binda, Giulio Rastelli, Isabella Rimoldi, Daniele Passarella, Maria Luisa Di Paolo, Lisa Dalla Via
Summary: A library of monosubstituted chalcones with electron-donating and electron-withdrawing groups on aromatic rings was selected for evaluation. Compounds 13 and 14 were found to inhibit MAO-B and may be worth considering as novel MAO-B-selective inhibitors for neurodegenerative disease treatment.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Physical
Laura Rotilio, Alexander Swoboda, Katharina Ebner, Claudia Rinnofner, Anton Glieder, Wolfgang Kroutil, Andrea Mattevi
Summary: HspUPO is a versatile unspecific peroxygenase that can tolerate selected organic solvents and perform various oxidation reactions, demonstrating a relatively broad substrate scope.
Editorial Material
Multidisciplinary Sciences
Andrea Mattevi
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Medicinal
Fredrik Ekstrom, Andrea Gottinger, Nina Forsgren, Marco Catto, Luca G. Iacovino, Leonardo Pisani, Claudia Binda
Summary: Multitarget directed ligands (MTDLs) are a promising approach to tackle the complexity of multifactorial pathologies. In the treatment of Alzheimer's disease, the synergistic inhibition of monoamine oxidase B (MAO B) and acetylcholinesterase (AChE) is believed to have a potentiated effect. Compound 1 showed tight-binding inhibition of MAO B and shape complementarity with the AChE enzymatic gorge, providing structural templates for the development of dual MAO B and AChE inhibitors.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Mario De Simone, Laura Alvigini, Lur Alonso-Cotchico, Vania Brissos, Jonatan Caroli, Maria Fatima Lucas, Emanuele Monza, Eduardo Pinho Melo, Andrea Mattevi, Ligia O. Martins
Summary: This study presents a new variant of the dioxygenase NOV1 that exhibits improved activity and stability compared to the wild type. The replacement of S283F in the variant leads to increased turnover rate and catalytic efficiency. The variant also demonstrates enhanced stabilization of the iron cofactor in the active site. Importantly, the variant is capable of catalyzing the conversion of isoeugenol to vanillin with high molar conversion yields within 24 hours.
Article
Biochemistry & Molecular Biology
Alessandro Boverio, Wahyu S. Widodo, Lars L. Santema, Henriette J. Rozeboom, Ruite Xiang, Victor Guallar, Andrea Mattevi, Marco W. Fraaije
Summary: In this study, the newly discovered carbohydrate oxidase NagOx from Ralstonia solanacearum was biochemically and structurally characterized. It showed high activity towards N-acetyl-D-galactosamine and N-acetyl-D-glucosamine, and could accept non-acetylated hexoses with lower efficiency. The crystal structure revealed a FAD-bound cavity and substrate docking highlighted a key residue involved in the accommodation of N-acetylated sugars. An enzyme variant with modified substrate acceptance profile was generated by replacing this residue. NagOx, being overexpressed in a bacterial host, has potential as a customizable biocatalyst for selective oxidation of monosaccharides and oligosaccharides.
Article
Multidisciplinary Sciences
Yiming Guo, Laura Alvigini, Milos Trajkovic, Lur Alonso-Cotchico, Emanuele Monza, Simone Savino, Andrea Mattevi, Marco W. Fraaije
Summary: Various 4-alkylphenols can be obtained from lignocellulosic biomass through reductive catalytic fractionation. This study presents the engineering of a bacterial eugenol oxidase to catalyze the selective dehydrogenation of 4-n-propylguaiacol to isoeugenol. The engineered variant shows good activity, thermostability, and high chemoselectivity.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Gautier Bailleul, Guang Yang, Callum R. R. Nicoll, Andrea Mattevi, Marco W. W. Fraaije, Maria Laura Mascotti
Summary: Enzyme functional diversification is crucial for biological adaptation, allowing organisms to utilize or eliminate new substances and xenobiotics in new environments. This study uses a paleobiochemistry approach and enzymology techniques to uncover the historical substitutions that led to the functional diversification of the FMO family in tetrapods. Few amino acid replacements modulate the oxygenating flavin intermediate, transforming an ancestral multi-tasking FMO into a specialized monooxygenase. This finding highlights the importance of residues beyond the active site core in determining enzymatic function. Detoxification enzymes play a crucial role in the survival of animals in new environments.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Callum R. Nicoll, Marta Massari, Marco W. Fraaije, Maria Laura Mascotti, Andrea Mattevi
Summary: Ancestral sequence reconstruction (ASR) is a powerful technique for understanding protein sequence changes across evolution and how they give rise to different phenotypes. It has been particularly useful in revealing common molecular factors governing enzyme function. This article highlights the strength of ASR in uncovering catalytic mechanisms and emerging phenotypes for various proteins, as well as its potential applications in biotechnology.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Gwen Tjallinks, Alessandro Boverio, Ivana Maric, Henriette Rozeboom, Mark Arentshorst, Jaap Visser, Arthur F. J. Ram, Andrea Mattevi, Marco W. Fraaije
Summary: Patulin synthase (PatE) from Penicillium expansum was expressed in Aspergillus niger, allowing purification and characterization of PatE. The study confirmed that PatE is active not only on ascladiol, but also on several aromatic alcohols including 5-hydroxymethylfurfural.
Article
Chemistry, Physical
Yiming Guo, Laura Alvigini, Mohammad Saifuddin, Ben Ashley, Milos Trajkovic, Lur Alonso-Cotchico, Andrea Mattevi, Marco W. Fraaije
Summary: This study presents a one-pot biocatalytic cascade reaction for the efficient synthesis of racemic syringaresinol, a valuable compound in nutraceutical and polymer chemistry. The process utilizes renewable lignocellulosic material and involves the engineering of enzymes to achieve high conversion and chemoselectivity. The study demonstrates the potential for the biocatalytic production of syringaresinol from renewable sources.
Article
Biochemistry & Molecular Biology
Gautier Bailleul, Callum R. Nicoll, Maria Laura Mascotti, Andrea Mattevi, Marco W. Fraaije
Summary: In this study, the ancestral protein sequences of FMO1 and FMO4 in mammals were reconstructed, and the structural analysis of AncFMO1 revealed typical FMO activities, providing insights into the catalytic properties of FMO1.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
