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
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)
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
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
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
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
Chemistry, Physical
Yann Mathieu, Maria E. Cleveland, Harry Brumer
Summary: Scientists have discovered a unique enzyme that can selectively oxidize alcohols to aldehydes and adapt to different carbohydrates. This finding has important implications for the design of improved biocatalysts.
Article
Chemistry, Physical
Yann Mathieu, Maria E. Cleveland, Harry Brumer
Summary: This study investigates the effect of deleting a specific loop in the active site of a Colletotrichum graminicola aryl alcohol oxidase on its catalytic activity, leading to changes in carbohydrate specificity and regiospecificity. The results highlight the catalytic adaptability of the mononuclear copper radical active site and provide a basis for designing improved biocatalysts for various applications.
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
Amy E. Medlock, Wided Najahi-Missaoui, Mesafint T. Shiferaw, Angela N. Albetel, William N. Lanzilotta, Harry A. Dailey
Summary: Ferrochelatase is an important enzyme involved in catalyzing heme synthesis in humans, serving a regulatory and catalytic role in the pathway. Studies on its crystal structures, kinetic properties, and catalytic cycle have provided insights into its functions. However, questions regarding metal ion delivery, active site residue roles, and the catalytic mechanism remain open for further investigation.
BIOCHEMICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Jacqueline Heger, Christine Hirschhaeuser, Julia Bornbaum, Akylbek Sydykov, Astrid Dempfle, Andre Schneider, Thomas Braun, Klaus-Dieter Schlueter, Rainer Schulz
Summary: The creation of MAO-B knockout mice demonstrates that the lack of cardiomyocyte MAO-B can protect the heart from I/R injury and reduce infarct size.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Bijo Mathew, Veerasamy Ravichandran, Seenivasan Raghuraman, T. M. Rangarajan, Mohamed A. Abdelgawad, Iqrar Ahmad, Harun M. Patel, Hoon Kim
Summary: This study utilized candidates generated from unsaturated ketone as potent, reversible, and specific MAO-B inhibitors, and identified several compounds with potential MAO-B inhibitory activity in the micro- to nanomolar range through the synthesis and evaluation of aldoxime-chalcone ethers and hydroxylchalcones. Molecular descriptors such as ETA Shape P and MDEO-12 were found to play significant roles in MAO-B inhibition, suggesting the possibility of creating potential chalcone-based MAO-B inhibitors with the current 2D QSAR models. Further analysis of lead molecules was conducted through detailed molecular dynamics study to confirm the stability of the ligand-enzyme complex.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Editorial Material
Chemistry, Physical
Etienne Derat, Shina Caroline Lynn Kamerlin
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Correction
Chemistry, Multidisciplinary
Rory M. Crean, Michal Biler, Marina Corbella, Ana R. Calixto, Marc W. van der Kamp, Alvan C. Hengge, Shina C. L. Kamerlin
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Physical
Martin Pfeiffer, Rory M. Crean, Catia Moreira, Antonietta Parracino, Gustav Oberdorfer, Lothar Brecker, Friedrich Hammerschmidt, Shina Caroline Lynn Kamerlin, Bernd Nidetzky
Summary: The cooperative interplay between functional devices in enzyme catalysis is important for understanding the efficiency of natural enzymes and enzyme design. This study investigates the functional interconnectedness of the catalytic nucleophile in an acid phosphatase and provides evidence for the cooperative interplay between nucleophilic and general-acid catalytic groups. The results show that the cooperative nature of enzymatic catalysis distinguishes it from the corresponding reaction in solution.
Editorial Material
Biochemistry & Molecular Biology
Shina Caroline Lynn Kamerlin
Editorial Material
Biochemistry & Molecular Biology
Adrian J. Mulholland, Shina Caroline Lynn Kamerlin
Summary: Is there a possibility of scientific collaboration between the UK and EU in the future?
Article
Chemistry, Medicinal
Lucija Hok, Robert Vianello
Summary: We used computational techniques to study the effect of selective C-H deuteration on the affinity of the antagonist istradefylline for the adenosine A2A receptor, comparing it with caffeine. Our results showed that istradefylline had a higher affinity than caffeine due to the additional C8-trans-styryl fragment and its lower hydration. Deuteration of the aromatic C8-unit further improved the affinity. We propose that this computational methodology can be used to estimate binding isotope effects in any biological system.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Physical
Rory M. Crean, Joanna S. G. Slusky, Peter M. Kasson, Shina Caroline Lynn Kamerlin
Summary: The simulation datasets of proteins contain information about how non-covalent interactions regulate the conformation and function of proteins. It would be valuable to be able to automatically process these datasets to identify non-covalent interactions associated with specific conformational changes. The Key Interactions Finder (KIF) is an open-source Python package that allows users to identify and rank non-covalent interactions relevant to a conformational change of interest.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Correction
Chemistry, Multidisciplinary
Marina Corbella, Gaspar P. Pinto, Shina C. L. Kamerlin
NATURE REVIEWS CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Marina Corbella, Gaspar P. Pinto, Shina C. L. Kamerlin
Summary: In the early 2000s, Tawfik proposed the 'New View' on enzyme evolution, emphasizing the role of conformational plasticity in expanding functional diversity. This concept is gaining support as more evidence emerges on the importance of conformational dynamics in enzyme evolution. Over the years, manipulating protein loop dynamics has been shown to be successful in altering protein function. This review focuses on the critical role of flexible loops in regulating enzyme activity and discusses the implications for engineering.
NATURE REVIEWS CHEMISTRY
(2023)
Editorial Material
Biochemistry & Molecular Biology
M. G. Finn, Shina Caroline Lynn Kamerlin
Article
Chemistry, Analytical
Ivana Novak Jovanovic, Robert Vianello, Dijana Jadresko, Livio Racane, Marijana Hranjec
Summary: This study reports on the electrochemical properties and antioxidant activity of four 2-hydroxy/methoxy-phenylbenzothiazole derivatives. The results show that two derivatives have the main electroactive center at the C6-amino group of the benzothiazole molecule, while the other two derivatives have the main electroactive center at the pyrogallol group.
JOURNAL OF ELECTROANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Anja Bec, Livio Racane, Lucija Zonja, Leentje Persoons, Dirk Daelemans, Kristina Starcevic, Robert Vianello, Marijana Hranjec
Summary: In this study, novel substituted coumarin-benzimidazole/benzothiazole hybrids with a cyclic amidino group on the benzazole core were designed and synthesized as biologically active agents. The prepared compounds were evaluated for their antiviral, antioxidative, and antiproliferative activities. Coumarin-benzimidazole hybrid 10 exhibited the most promising broad spectrum antiviral activity, while hybrids 13 and 14 demonstrated the highest antioxidative capacity. Computational analysis supported these results and showed the importance of the cationic amidine unit and the electron-donating diethylamine group in the coumarin core. The substitution of the coumarin ring at position 7 with a N,N-diethylamino group also enhanced the antiproliferative activity, with derivatives 13 and 18 being the most active.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Alessandro Crnjar, Aransa Grinen, Shina C. L. Kamerlin, Cesar A. Ramirez-Sarmiento
Summary: PET is a common plastic in packaging industry and contributes to environmental pollution. IsPETase enzyme has optimal activity at 30-35°C and inserting its unique residues S214/I218 into other PET hydrolases enhances activity and decreases optimal conditions.
ACS ORGANIC & INORGANIC AU
(2023)
Article
Chemistry, Multidisciplinary
Mia Radovic, Lucija Hok, Manuela Panic, Marina Cvjetko Bubalo, Robert Vianello, Marijana Vinkovic, Ivana Radojcic Redovnikovic
Summary: This study reports the stabilisation of nicotinamide adenine dinucleotide (NAD) coenzyme using deep eutectic solvents (DES). Through DES screening and computational analysis, choline chloride:urea (ChCl:U) was identified as the best solvent for stabilising both NAD forms. The NAD in ChCl:U showed prolonged stability in a model enzymatic assay.
Article
Chemistry, Multidisciplinary
Lucija Hok, Robert Vianello, Dubravka Matkovic-Calogovic, Ljitjana Karanovic, Sundica Roca, Jaroslaw Jazwinski, Manna Tasner, Darko Vusak, Manjana Dakovic, Zora Popovic
Summary: In this study, seven nickel(II) thiocyanate complexes were synthesized and their crystal structures and coordination modes were investigated under varying isonicotinamide concentrations. They were characterized by single-crystal X-ray diffraction and DFT calculations, and some complexes were also analyzed using NMR and IR spectroscopy.