Article
Chemistry, Multidisciplinary
Vladimir N. Ivanov, Mariangela Agamennone, Ildar R. Iusupov, Antonio Laghezza, Anton M. Novoselov, Ekaterina Manasova, Andrea Altieri, Paolo Tortorella, Alexander A. Shtil, Alexander Kurkin
Summary: This study developed new compounds based on the isatin scaffold, showing activity against MMP-2 and MMP-13 with reduced or negligible activity against MMP-8. Substitution of the isatin ring did not decrease potency against MMP-13 but reduced selectivity.
ARABIAN JOURNAL OF CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Helena Laronha, Ines Carpinteiro, Jaime Portugal, Ana Azul, Mario Polido, Krasimira T. Petrova, Madalena Salema-Oom, Isabel Barahona, Jorge Caldeira
Summary: A new class of MMP inhibitors has been discovered, which can be co-polymerized with other vinyl compounds in commercial dental resins, limiting release and potential toxicity, and increasing safety. These inhibitors show unique properties towards various MMPs and did not significantly decrease cell viability at high concentrations.
Article
Biochemistry & Molecular Biology
Alessandro Bonadio, Solomon Oguche, Tali Lavy, Oded Kleifeld, Julia Shifman
Summary: Matrix metalloproteinase-9 (MMP-9) is an unstable enzyme implicated in various diseases. In this study, a stable variant of MMP-9Cat was designed by identifying and eliminating auto-cleavage sites. The best variant, Des2, showed no auto-cleavage and retained enzyme activity, making it suitable for drug design and crystallization experiments. This strategy can be applied to stabilize other proteases for biotechnological applications.
BIOCHEMICAL JOURNAL
(2023)
Article
Chemistry, Organic
Fangqing Zhang, Bing-Tao Ren, Yangbin Liu, Xiaoming Feng
Summary: In this study, an asymmetric inverse-electron-demand Diels-Alder reaction catalyzed by a chiral catalyst was developed for the synthesis of Cephalotaxus norditerpenoids with densely functionalized hexahydrofluorenyl bridged-lactone scaffold. The reaction showed high yields and enantioselectivities under mild conditions.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Biochemistry & Molecular Biology
Jose Maria Zapico, Lourdes Acosta, Miryam Pastor, Loganathan Rangasamy, Laura Marquez-Cantudo, Claire Coderch, Irene Ortin, Maria Nicolau-Sanus, Leonor Puchades-Carrasco, Antonio Pineda-Lucena, Alejandro Majali-Martinez, Pilar Ramos, Beatriz de Pascual-Teresa, Ana Ramos
Summary: This study focuses on exploring a new treatment for osteoarthritis by inhibiting MMP-13 to prevent disease progression, identifying a potential inhibitor with promising activity. The results show that compound 9a has good solubility and inhibitory activity, making it suitable for use in MG-63 human osteosarcoma cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Benjamin S. Frank, Debmalya Nandy, Ludmila Khailova, Max B. Mitchell, Gareth J. Morgan, Mark Twite, Michael V. Dimaria, Jesse A. Davidson
Summary: Children with single ventricle heart disease (SVHD) experience morbidity due to inadequate pulmonary blood flow. Previous research has identified potential dysregulation of MMP, TIMP, and FGF protein families in SVHD. In this study, we conducted a prospective cohort study to investigate the levels of 39 proteins in these families in SVHD infants. We found that 20 out of the 39 tested proteins differed between SVHD cases and healthy controls. Additionally, we identified specific proteins that were associated with post-Stage 2 hypoxemia and length of stay. Our findings suggest that ECM protein imbalance may play a crucial role in SVHD.
SCIENTIFIC REPORTS
(2023)
Review
Pharmacology & Pharmacy
Kang Fu, Xueyao Zheng, Yuhan Chen, Liuying Wu, Zhiming Yang, Xu Chen, Wei Song
Summary: Diabetic foot ulcers (DFUs) are serious complications of diabetes mellitus, characterized by tissue destruction in the foot. Matrix metalloproteinases (MMPs) play crucial roles in the pathogenesis and wound healing process of DFUs. Overexpression of MMPs in DFUs can result in excessive tissue degradation and impaired wound healing. Regulation of MMP levels may facilitate wound healing in DFUs.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Youhai Tan, Lingxue Dai, Weifeng Huang, Yinfeng Guo, Shuangjia Zheng, Jinping Lei, Hongming Chen, Yuedong Yang
Summary: A novel framework called DRlinker was proposed in this study to control fragment linking and generate compounds with specified attributes through reinforcement learning. The method has been demonstrated to be effective in various tasks, including controlling linker length and log P, optimizing predicted bioactivity of compounds, and achieving various multiobjective tasks.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Youhai Tan, Lingxue Dai, Weifeng Huang, Yinfeng Guo, Shuangjia Zheng, Jinping Lei, Yuedong Yang, Hongming Chen
Summary: In this study, a novel framework called DRlinker was proposed to control fragment linking for generating candidate compounds with specified attributes using reinforcement learning. The method has been proven effective for various tasks, including controlling linker length and log P, optimizing predicted bioactivity of compounds, and handling multiple objectives.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Organic
Zhenzhu Hu, Peng Ma, Ning Ma, Jianhui Wang
Summary: A new FeCl3-catalyzed strategy using 1H-indene-1,2,3-triones and alkynes as starting materials is reported for the synthesis of various tanshinlactone derivatives. This protocol offers the advantages of low cost, environmentally benign catalysts, simple reaction conditions, and a broad range of substrates.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Zheng Liang, Jibin Li, Lei Wang, Zexuan Wei, Jiahui Huang, Xinrui Wang, Ding Du
Summary: A new synthesis of functionalized 2H-pyran-2-ones has been developed through N-heterocyclic carbene-catalyzed formal [3 + 3] annulation of alkynyl esters with enolizable ketones. The key to the success of this protocol relies on the use of an NHC instead of a tertiary amine as the catalyst. This protocol also features a broad substrate scope and mild metal-free conditions, offering simple and rapid access to the target molecules in a highly regioselective manner.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Review
Food Science & Technology
Luciana Azevedo, Daniel Granato, Vinicius Maltarollo, Jose E. Goncalves
Summary: Agrifood system technologies have facilitated the creation of innovative foods with improved nutritional profiles. This article provides an overview of the development of food models/prototypes using natural compounds as a source of inspiration, through the integration of various disciplines and food technologies. To create healthy foods, the combination of interrelated technologies from nutrition, chemical synthesis, pharmacology, and food technology with biological system analyses is proposed. Developing food molecules is a slow process that involves mandatory steps based on desired bioactive properties, which is hindered by the diversity of food matrices and the complexity of reconstituting their biosynthetic pathways. Overcoming these challenges should be a primary focus in food science, leading to more sustainable processes and health benefits.
CURRENT OPINION IN FOOD SCIENCE
(2023)
Article
Engineering, Environmental
Shuo Xiang, Jia Liu, Guangze Han, Wei Zhang, Yanyang Long, Yuxian Deng, Binju Wang, Qunhong Weng
Summary: Cell nucleus is the ultimate target for therapeutic agents in disease treatments. A novel 1D semiconducting zinc coordination polymer (Zn-QCDM) was designed to target the nucleus, showing selective targeting of nucleoli with the selectivity over 40%. When loaded with the chemotherapeutic drug camptothecin (CPT), the Zn-QCDM effectively delivers the drug to the nucleus and significantly enhances the therapeutic effect.
CHEMICAL ENGINEERING JOURNAL
(2023)
Article
Chemistry, Organic
Zheng Liang, Jibin Li, Lei Wang, Zexuan Wei, Jiahui Huang, Xinrui Wang, Ding Du
Summary: A new method for the synthesis of functionalized 2H-pyran-2-ones has been developed, using N-heterocyclic carbene-catalyzed formal [3 + 3] annulation of alkynyl esters with enolizable ketones. The use of NHC instead of a tertiary amine as the catalyst is crucial for the success of this protocol, which offers a wide range of substrate options and mild metal-free conditions, allowing for the simple and rapid access to the target molecules in a highly regioselective manner.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Anna Surowka, Piotr Prowans, Michal Zolnierczuk, Marek Miskiewicz, Tomasz Wawrowski, Marika Skodda, Marta Markowska, Karolina Kedzierska-Kapuza
Summary: This review discusses the role of metalloproteinases in myocardial injury in various diseases, examining changes in their expression and serum levels, as well as the impact of immunosuppressive treatment. The study focuses on the use of calcineurin inhibitors and their potential side effects on the cardiovascular system. The research emphasizes the importance of expanding knowledge on this subject and minimizing negative effects of post-transplant therapy. It also analyzes the effects of specific heart diseases on myocardial remodeling through the involvement of matrix metalloproteinases and their inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Moritz K. Jackl, Hyeonglim Seo, Johannes Karges, Mark Kalaj, Seth M. Cohen
Summary: Metalloenzyme inhibitors typically require a metal-binding pharmacophore (MBP), but MBPs can have limitations. In this study, a total of 27 salicylate metal-binding isosteres (MBIs) were synthesized as replacements for the carboxylic and hydroxyl group of the salicylic acid MBP. These salicylate MBIs were characterized for their metal-binding features, physicochemical properties, and biological activity. The results showed that salicylate MBIs can have attractive physicochemical properties and maintain or improve enzyme inhibition and selectivity.
Article
Chemistry, Organic
Johannes Karges, Seth M. Cohen
Summary: A new type of receptor molecule based on a tripodal tris(pyrrolamide) motif is presented in this study, which can bind to various anions with high affinity. The study demonstrates the ability to differentiate between enantiomeric anions through the preorganized cavity structure of the receptors.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Inorganic & Nuclear
Hyeonglim Seo, Moritz K. Jackl, Mark Kalaj, Seth M. Cohen
Summary: The use of metal-binding pharmacophores (MBPs) in drug discovery is effective for developing metalloenzyme inhibitors. 8-HQ and its derivatives are important MBPs with tunable physicochemical properties.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Johannes Karges, Ryjul W. Stokes, Seth M. Cohen
Summary: In this study, a technique for predicting the binding pose of metal-binding pharmacophores (MBPs) was proposed. By combining density functional theory (DFT) calculations and docking using a genetic algorithm, the binding of inhibitors was evaluated in silico and compared with experimental results. The computational strategy presented in this study is a useful tool for predicting metalloenzyme-MBP interactions.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Nanoscience & Nanotechnology
Dong Ju Lee, Xiaolu Yu, R. Eric Sikma, Mingqian Li, Seth M. Cohen, Zheng Chen, Guorui Cai
Summary: Metal-organic framework (MOF)-based membranes have been extensively studied as separators for lithium-sulfur (Li-S) batteries. This research investigates the property-performance relationship between MOF-based separators and Li-S batteries by adjusting the electrical conductivity, thickness, and mass loading of the MOF-based composite. The study found that the electrical conductivity of the MOF composite layer is more important than the physical/chemical trapping ability of polysulfides when the thickness is fixed. However, the trapping ability of MOFs becomes indispensable at smaller thickness, indicating the synergetic effects of the adsorption and conversion capabilities of the thin composite layer. This work highlights the importance of a holistic design consideration for MOF-based membranes in long-life and high-energy-density Li-S batteries.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Review
Chemistry, Multidisciplinary
R. Eric Sikma, Krista P. Balto, Joshua S. Figueroa, Seth M. Cohen
Summary: This Minireview discusses recent advances in low-valent MOFs and provides insights into future developments of these materials.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Inorganic & Nuclear
Ryan A. Dodson, Junkil Park, Jihan Kim, Matthew J. Cliffe, Seth M. Cohen
Summary: This study used oligomeric ligand precursors to prepare oligomeric-linker MOFs based on the prototypical IRMOF-1 system. It was found that IRMOF-1 was highly tolerant to oligomeric linkers and exhibited tether length-dependent ordering of ligand and metal cluster orientations. Additionally, improved low-humidity stability was observed in oligoIRMOF-1 samples.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Hyeonglim Seo, Alysia J. J. Kohlbrand, Ryjul W. W. Stokes, Jeewon Chung, Seth M. M. Cohen
Summary: Thioamides, thioureas, and thiocarbamates are introduced as stable metal-binding pharmacophores for use in metalloenzyme fragment-based drug discovery. Studies show that these molecules can act as ligands for Zn(ii)-dependent metalloenzymes including human carbonic anhydrase II and matrix metalloproteinase-2.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Conor B. O'Herin, Yuta W. Moriuchi, Troy A. Bemis, Alysia J. Kohlbrand, Michael D. Burkart, Seth M. Cohen
Summary: Human carbonic anhydrase II (hCAII) is a vital metalloenzyme in the human body, and its inhibitors have clinical applications in treating various diseases. This study developed degrader candidates targeting hCAII, which showed promising potential in inducing the degradation of hCAII. Optimization of the candidates resulted in a highly potent degrader with sustained depletion of hCAII. Mechanistic studies indicated that this optimized degrader functions similarly to previously reported CRBN-recruiting degraders.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Johannes Karges, Miriam A. Giardini, Olivier Blacque, Brendon Woodworth, Jair L. Siqueira-Neto, Seth M. Cohen
Summary: Functionalized Re(i) tricarbonyl complexes were synthesized and found to inhibit the activity of the SARS-CoV-2 main protease, presenting a potential antiviral strategy.
Letter
Chemistry, Medicinal
Ryjul W. Stokes, Alysia J. Kohlbrand, Hyeonglim Seo, Banumathi Sankaran, Johannes Karges, Seth M. Cohen
Summary: In this study, various metal-binding isosteres (MBIs) were examined to modulate the activity of the RNA-dependent RNA polymerase acidic N-terminal (PAN) endonuclease. The inhibitory ability of MBIs against PAN was evaluated using a FRET-based enzymatic assay, and their binding mode in PAN was determined using X-ray crystallography.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Samuel E. Griffin, Grant P. Domecus, Clarissa E. Flores, R. Eric Sikma, Lauren Benz, Seth M. Cohen
Summary: Low-valent metal-organic frameworks (LVMOFs) and related materials have potential applications in heterogeneous catalysis, but no catalytic activity has been observed in the reported LVMOFs. In this study, a low-valent metal-organic material constructed from phosphine linkers and Ir-I nodes is reported. This material, similar to Vaska's complex, can reversibly bind O-2 and catalyze the reductive formation of enamines from amides.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Medicinal
Johannes Karges, Seth M. Cohen
Summary: Interest in covalent enzyme inhibitors as therapeutic agents has recently increased. In this article, the use of small, modular ReV complexes as inorganic cysteine-targeting warheads is described. These metal complexes were found to react rapidly and selectively with cysteine residues. The utility of these ReV complexes was demonstrated by their inhibition of SARS-CoV-2-associated cysteine proteases and human enzymes cathepsin B and L through the formation of adducts.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Austin Wang, Kyle Barcus, Seth M. Cohen
Summary: The surface chemistry of three MOFs, UiO-66, MIL-88B-NH2, and ZIF-8, was investigated using dye-displacement experiments. Ligand affinity on the MOF surface was found to be dependent on the metal-ligand composition. This work provides important insights for the modulation, modification, and manipulation of MOFs.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Physical
Prantik Mondal, Zhaoxi Zheng, Klaus Schmidt-Rohr, Seth M. Cohen
Summary: Postsynthetic modification (PSM) is an important tool for functionalizing metal-organic frameworks (MOFs). However, the availability of organic linkers with readily modified functional groups remains a challenge. In this study, a benzene dicarboxylic acid with azidomethyl groups was synthesized and introduced into two different MOF structures. The pendant alkyl azide groups in these MOFs were amenable to PSM via click reactions. Furthermore, the pore size restriction in one of the MOFs could be overcome by using a mixed ligand approach. Importantly, the azidomethyl groups could be reduced to primary benzylic amines, maintaining the crystallinity and porosity of the MOF.
CHEMISTRY OF MATERIALS
(2023)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)