Article
Biochemistry & Molecular Biology
Alessandro Grillo, Filomena Fezza, Giulia Chemi, Roberto Colangeli, Simone Brogi, Domenico Fazio, Stefano Federico, Alessandro Papa, Nicola Relitti, Roberto Di Maio, Gianluca Giorgi, Stefania Lamponi, Massimo Valoti, Beatrice Gorelli, Simona Saponara, Mascia Benedusi, Alessandra Pecorelli, Patrizia Minetti, Giuseppe Valacchi, Stefania Butini, Giuseppe Campiani, Sandra Gemma, Mauro Maccarrone, Giuseppe Di Giovanni
Summary: Research has discovered new FAAH inhibitors with promising antiepileptic efficacy and devoid of psychotropic effects. These inhibitors showed good results in animal models, prompting further investigation for potential new antiepileptic agents.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Chemistry, Medicinal
Alessandro Papa, Silvia Pasquini, Francesca Galvani, Mariarosaria Cammarota, Chiara Contri, Gabriele Carullo, Sandra Gemma, Anna Ramunno, Stefania Lamponi, Beatrice Gorelli, Simona Saponara, Katia Varani, Marco Mor, Giuseppe Campiani, Francesca Boscia, Fabrizio Vincenzi, Alessio Lodola, Stefania Butini
Summary: The neuroprotective performance of the endocannabinoid system (ECS) against neuroinflammation can be significantly enhanced by inhibiting the key ECS enzyme FAAH. In this study, a series of carbamate-based FAAH inhibitors were developed with improved drug properties compared to previous analogues. These inhibitors showed nanomolar potency, good water solubility, and chemical stability. They exhibited excellent selectivity against monoacylglycerol lipase and cannabinoid receptors, and demonstrated reversible mechanisms of action without toxicity or cardiac effects. Selected analogues displayed notable neuroprotective effects against oxidative stress and neuroinflammation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Mahdi Faal Maleki, Hamid Nadri, Mostafa Kianfar, Najmeh Edraki, Farhad Eisvand, Razieh Ghodsi, Seyed Ahmad Mohajeri, Farzin Hadizadeh
Summary: New carbamates were designed as inhibitors of FAAH and ChEs in order to improve the clinical condition of AD patients. Compounds with aminomethyl phenyl linker showed more potent inhibitory activity compared to those with piperazinyl ethyl linker.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Elham Rezaee, Somayeh Minaei Amrolah, Maryam Nazari, Sayyed Abbas Tabatabai
Summary: The study focused on designing, synthesizing and evaluating new amide-based derivatives of 3-phenylglutaric acid as potential sEH inhibitors. Most of the synthesized compounds showed nanomolar range inhibition against sEH enzyme, with the best observed IC50 value of 0.5 nM. Incorporating carboxylic moieties into the structures could increase solubility and improve physicochemical properties.
MOLECULAR DIVERSITY
(2021)
Review
Chemistry, Medicinal
Shivani Jaiswal, Senthil Raja Ayyannan
Summary: Recently, FAAH and MAGL inhibitors have attracted attention for their potential anticancer effects. By regulating endogenous ligands, these inhibitors show therapeutic effects in chronic pain, metabolic disorders, psychoses, among others, and exhibit potential in various types of cancers.
Article
Chemistry, Medicinal
Shivani Jaiswal, Senthil Raja Ayyannan
Summary: By utilizing a ligand-based design strategy, a series of isatin-3-carbohydrazones were synthesized and evaluated for their dual FAAH and MAGL inhibition properties. The study identified potent inhibitors, with compounds 13b and 13j being the most effective against MAGL and FAAH respectively, while compound 13c exhibited dual inhibitory activity and significant antioxidant properties in cell-based assays. These compounds showed promising pharmacokinetic profiles for treating neurological and mood disorders.
Article
Chemistry, Medicinal
Shivani Jaiswal, Garima Gupta, Senthil R. Ayyannan
Summary: This study designed and synthesized a series of carbamate compounds and evaluated their dual FAAH-MAGL inhibition properties. Compound 2e, 3h, and 2i showed the strongest inhibitory effects. Enzyme kinetics experiments revealed that these compounds inhibit FAAH/MAGL in a mixed binding mode of covalent-reversible manner. Additionally, docking simulation experiments and ADMETox prediction studies provided useful information for further investigation.
ARCHIV DER PHARMAZIE
(2022)
Article
Infectious Diseases
Alessia Catalano, Antonio Rosato, Lara Salvagno, Domenico Iacopetta, Jessica Ceramella, Giuseppe Fracchiolla, Maria Stefania Sinicropi, Carlo Franchini
Summary: Triclocarban is a widely used antimicrobial agent with potential environmental impact. Researchers have been studying the synthesis and biological activity of new compounds to replace TCC, and some analogues have shown higher antimicrobial activity against bacteria such as Staphylococcus aureus and Enterococcus faecalis. Compound 2bG also exhibited interesting bactericidal action despite being less active than others.
Article
Biochemistry & Molecular Biology
Sanela Rajlic, Luise Surmann, Pia Zimmermann, Christina Katharina Weisheit, Laura Bindila, Hendrik Treede, Markus Velten, Andreas Daiber, Georg Daniel Duerr
Summary: Ischemic cardiomyopathy leads to inflammation and left ventricular dysfunction. Animal studies suggest that the endocannabinoid system may have cardioprotective effects, including cardiomyocyte adaptation, inflammation, and remodeling. This study investigates the potential cardioprotective effect of the endocannabinoid anandamide (AEA) after ischemia and reperfusion using FAAH (-/-) mice and suggests that increased endocannabinoids may have detrimental effects on cardiomyocyte survival due to PPAR-alpha activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Chaoling Chen, Weili Wang, Justin L. Poklis, Aron H. Lichtman, Joseph K. Ritter, Gaizun Hu, Dengpiao Xie, Ningjun Li
Summary: The study suggests that FAAH activation and the consequent reduction of AEA contribute to renal fibrogenesis, while FAAH inhibition protects against fibrogenesis in renal cells independently of CB receptors via the AEA-COX-2 pathway.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Veterinary Sciences
Vikram Thakur, Mohammad Bashashati, Josue Enriquez, Munmun Chattopadhyay
Summary: This study assessed specific gastrointestinal symptoms in Type 1 diabetic mice and evaluated treatment options for this condition. The results showed that inhibiting endocannabinoid degradation may have a therapeutic effect on gastrointestinal dysmotility.
VETERINARY SCIENCES
(2022)
Article
Chemistry, Medicinal
Xiaoyuan Li, Yuexiang Li, Shiyong Fan, Ruiyuan Cao, Xiaojia Li, Xiaomeng He, Wei Li, Longfa Xu, Tong Cheng, Honglin Li, Wu Zhong
Summary: A series of novel quinoline analogues targeting VP1 were identified as potent anti-EV-D68 agents through virtual screening and rational design. Compound 19 exhibited strong antiviral activity against various EV-D68 strains and inhibited viral replication. Mechanistic studies indicated that these anti-EV-D68 agents mainly work by interacting with VP1.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Anitha Police, Vijay Kumar Shankar, Pankaj Pandey, Srinath Rangappa, Robert J. Doerksen, S. Narasimha Murthy
Summary: Peripheral neuropathy (PN) is a condition characterized by peripheral nerve damage leading to severe pain. The current treatments for PN have either psychotropic side effects or are not effective enough. This study aims to find a safe inhibitor of the fatty acid amide hydrolase enzyme (FAAH) and develop a topical gel formulation to deliver anandamide, an endocannabinoid that relieves PN pain. The results showed that silymarin constituents, particularly silybin, demonstrated significant FAAH inhibition potential and increased the half-life of anandamide. The developed gel formulation increased the permeation of anandamide and silybin, resulting in a significant increase in pain threshold in rat models of PN.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Shivani Jaiswal, Akhilesh, Ankit Uniyal, Vinod Tiwari, Senthil Raja Ayyannan
Summary: Researchers have discovered a promising lead compound for the treatment of neuropathic pain by designing and synthesizing a series of compounds. The lead compound exhibited potent inhibition activity against both FAAH and MAGL, and showed good safety profile in vivo experiments.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ziad Omran
Summary: Novel disulfiram derivatives were evaluated as potent inhibitors of MAGL, showing high selectivity over FAAH. Compound 2i displayed low micromolar inhibition of MAGL without inhibitory activity against FAAH.