Article
Biochemistry & Molecular Biology
O. M. Hendawy, Hesham A. M. Gomaa, Sami Alzarea, Mutariah S. Alshammari, Fatma A. M. Mohamed, Yaser A. Mostafa, Ahmed H. Abdelazeem, Mostafa H. Abdelrahman, Laurent Trembleau, Bahaa G. M. Youssif
Summary: New series of COX-2/sEH inhibitors were synthesized to replace withdrawn COX-2 selective drugs, with promising analgesic, anti-inflammatory effects and lower cardiotoxicity. Compounds 20, 22, and 29 showed significant COX-2 inhibitory activity and were the most potent dual COX-2/sEH inhibitors, demonstrating good analgesic/anti-inflammatory effects and cardioprotective properties in vivo studies.
BIOORGANIC CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Zhiran Ju, Menglan Li, Junde Xu, Daniel C. Howell, Zhiyun Li, Fen-Er Chen
Summary: Cyclooxygenases play a vital role in inflammation, but currently used anti-inflammatory drugs have associated adverse effects. Researchers are searching for novel selective COX-2 inhibitors.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Chemistry, Organic
Qing-Hu Teng, Gui-Xia Sun, Shu-Ying Luo, Kai Wang, Fu-Pei Liang
Summary: Novel 1,5-diaryl substituted pyrazole secnidazole ester derivatives exhibited promising inhibitory activities against multiple tumor cell lines, with lower IC50 values against liver tumor cells. These compounds show potential in the field of anticancer treatment and demonstrate relative safety for normal cell lines.
JOURNAL OF HETEROCYCLIC CHEMISTRY
(2021)
Article
Chemistry, Physical
Musa El-Barghouthi, Ayman S. Hasan, Wajdy Al-Awaida, Hamzeh J. Al-Ameer, Jatinder Kaur, Kaita J. Hayashibara, Jeremy Fleming, Jessica Waknin, Shigeo Hayashibara, Muna Slewa, Samer M. Hamzeh, Khaled Bodoor, Joshua Daniel McLoud, Frank Wuest, Baker Jawabrah Al Hourani
Summary: A unique class of 1,5-disubstituted tetrazoles were designed and synthesized, showing enhanced inhibition potency towards COX-2 enzyme. Tetrazole 4 exhibited the highest inhibition potency for both COX-2 and COX-1 enzymes while displaying selectivity for COX-2. Among the compounds studied, only azole 5 showed anti-cancer activity against human immortalized myelogenous leukemia. Overall, the investigated compounds showed low cytotoxicity for HDFa cell lines.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Immunology
Josyelen L. Felipe, Iluska S. Bonfa, Paloma K. M. B. Lossavaro, Joyce S. Lencina, Diego B. Carvalho, Luciane Candeloro, Giovanni I. S. Ferreira, Amarith R. das Neves, Maria Ines L. Souza, Saulo E. Silva-Filho, Adriano C. M. Baroni, Monica C. Toffoli-Kadri
Summary: This study found that synthesized hybrid triazole analogs have anti-inflammatory effects on arthritis, reducing symptoms without side effects, and may serve as potential therapeutic prototypes for treating rheumatoid arthritis.
INFLAMMOPHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Minakshi A. Meshram, Utkarsha O. Bhise, Priyanka N. Makhal, Venkata Rao Kaki
Summary: Inflammation is a complex pathological process leading to various diseases, with different treatments available but limitations exist. The development of new, effective, and safe anti-inflammatory agents is needed to address the shortcomings of current treatments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Goutami G. Ambati, Sanjay M. Jachak
Summary: This review highlights 158 natural product inhibitors of COX from 2006 to 2019, encompassing various secondary metabolite classes from plant and marine sources. These COX inhibitors have significant potential in drug discovery, particularly in cancer chemoprevention.
CURRENT MEDICINAL CHEMISTRY
(2021)
Review
Oncology
Mohammad Mahboubi-Rabbani, Maryam Abbasi, Afshin Zarghi
Summary: Cyclooxygenase-2 (COX-2) is an important enzyme in cancer development and a target of interest for drug designers. However, prolonged use of COX-2 inhibitors is associated with life-threatening cardiovascular side effects. This review explores the potential of natural secondary metabolites as COX-2 inhibitors and their ability to inhibit cancer development.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2023)
Review
Oncology
Mohammad Mahboubi-Rabbani, Maryam Abbasi, Afshin Zarghi
Summary: Cyclooxygenase-2 (COX-2) is an enzyme that plays a crucial role in cancer development. However, prolonged use of COX-2 inhibitors may have life-threatening cardiovascular side effects. By modifying the structures of natural secondary metabolites, COX-2 selective inhibitors with limited side effects and comparative efficacy can be developed. Therefore, researchers are exploring natural organic scaffolds as leads for new COX-2 inhibitors.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Lijun Xie, Renfu Li, Biyun Zheng, Zuoxu Xie, Xuefen Fang, Yanqi Wang, Gregory D. Cuny, Zhenli Li, Bin Lin, Xueyuan Chen, Ming Hu
Summary: A new class of COX-2-specific fluorescent probes has been developed in this study with attractive fluorescence properties, showing potential for identifying COX-2 in cancer cells and tissues.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Grigoriy V. V. Urakov, Konstantin V. V. Savateev, Svetlana K. K. Kotovskaya, Vladimir L. L. Rusinov, Alexandr A. A. Spasov, Denis A. A. Babkov, Elena V. V. Sokolova
Summary: The study focuses on the synthesis and structure-activity relationship of 6-(tetrazol-5-yl)-7-aminoazolo[1,5-a]pyrimidines as inhibitors of Casein kinase 2 (CK2); The desired compounds showed significant CK2 inhibition, with the leader compound displaying an IC50 of 45 nM.
Article
Chemistry, Medicinal
Mario Saletti, Samuele Maramai, Annalisa Reale, Marco Paolino, Simone Brogi, Angela Di Capua, Andrea Cappelli, Gianluca Giorgi, Danilo D'Avino, Antonietta Rossi, Carla Ghelardini, Lorenzo Di Cesare Mannelli, Roccaldo Sardella, Andrea Carotti, Gerald Woelkart, Burkhard Klosch, Chiara Bigogno, Giulio Dondio, Maurizio Anzini
Summary: The design of compounds that selectively inhibit COX-2 and release NO is a promising strategy for developing potent anti-inflammatory agents with reduced gastrointestinal and cardiovascular toxicity. The results showed that the isosteric substitution of the ethereal oxygen atom with sulfur led to the synthesis of new selective and highly potent COX-2 inhibitors, capable of inducing vasorelaxant responses. These compounds also demonstrated significant efficacy in mouse models of inflammation and pain.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Maurizio Anzini, Mario Saletti, Samuele Maramai, Annalisa Reale, Marco Paolino, Simone Brogi, Angela Di Capua, Andrea Cappelli, Gianluca Giorgi, Danilo D'Avino, Antonietta Rossi, Carla Ghelardini, Lorenzo Di Cesare Mannelli, Roccaldo Sardella, Andrea Carotti, Gerald Woelkart, Burkhard Klosch, Chiara Bigogno, Giulio Dondio
Summary: The design of compounds that selectively inhibit COX-2 and release NO is a promising strategy for developing potent anti-inflammatory drugs with reduced gastrointestinal and cardiovascular toxicity. By substituting the oxygen atom with a sulfur atom, new selective and highly potent COX-2 inhibitors can be synthesized, capable of inducing vasorelaxation in vivo.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Organic
Nikita I. Efimenko, Olesya A. Tomashenko, Dar'ya V. Spiridonova, Mikhail S. Novikov, Alexander F. Khlebnikov
Summary: 2H-azirine-2-carbonyl azides undergo rearrangement into derivatives of 2-(1H-tetrazol-1-yl)acetic acid when interacting with O- and S-nucleophiles at room temperature. The reaction is catalyzed by tertiary amines or hydrazoic acid. Different reactions occur when interacting with primary alcohols and phenols, leading to the formation of alkyl/aryl 2-(1H-tetrazol-1-yl)acetates. Additionally, thiophenols react with 2H-azirine-2-carbonyl azides to produce S-aryl 2-(1H-tetrazol-1yl)ethanethioates. The mechanism of these nucleophile-induced rearrangements is discussed based on DFT calculations, kinetic experiments, and N-15 labeling experiments.
Review
Medical Laboratory Technology
Wanjun Li, Zhiwei Zhang, Baiyun Wang, Na Liang, Qier Zhou, Songkai Long
Summary: Breast cancer is among the most common cancers in women worldwide, and miRNAs and COX-2 are new diagnostic and therapeutic biomarkers for monitoring BC. COX-2 is associated with tumor growth and metastasis, while MiRs show differential expression in breast tumor tissue. Understanding the pathway between miRNAs and COX-2 can lead to the development of new therapeutic approaches for BC.
CLINICA CHIMICA ACTA
(2021)
Review
Pharmacology & Pharmacy
Matthew T. J. Halma, Jack A. Tuszynski, Gijs J. L. Wuite
Summary: The time and cost of developing new therapeutic drugs is a significant burden, involving computational screening, compound assays, and expensive clinical trials. This review highlights the value of dynamic conformational information obtained through optical tweezers for targeting "undruggable" proteins. Optical tweezers provide insights into the relationship between biological mechanisms and structural conformations, aiding in drug discovery. Developing workflows and tools for optical tweezers will improve efficiency, allowing for greater adoption in the biopharmaceutical industry. As a complementary tool, optical tweezers increase the number of potential drug candidates, enhance understanding of a target's complex structural dynamics, and elucidate compound-target interactions.
DRUG DISCOVERY TODAY
(2023)
Article
Medicine, Research & Experimental
Martin Ullrich, Susan Richter, Josephine Liers, Stephan Drukewitz, Markus Friedemann, Joerg Kotzerke, Christian G. Ziegler, Svenja Noelting, Klaus Kopka, Jens Pietzsch
Summary: This study evaluates the effects of epigenetic drugs on SSTR2 levels and sensitivity to [177Lu]Lu-DOTA-TATE in mouse pheochromocytoma models, and found that epigenetic drugs have a therapeutic benefit, although the exact mechanism is unknown.
Article
Pharmacology & Pharmacy
Sebastian Braun, Svetlana Paskas, Markus Laube, Sven George, Bettina Hofmann, Peter Loennecke, Dieter Steinhilber, Jens Pietzsch, Sanja S. Mijatovic, Danijela Maksimovic-Ivanic, Evamarie Hey-Hawkins
Summary: In this study, carborane-containing dual COX-2/5-LO inhibitors were designed by incorporating metabolically stable, sterically demanding, and hydrophobic carboranes into existing inhibitors. Five carborane-containing derivatives showed high inhibitory activities towards COX-2 and 5-LO, with meta-carborane derivative 3 demonstrating higher anticancer activity compared to RWJ-63556. The accumulation of lipid droplets in cells indicated the blockage of COX-2 and 5-LO pathways, suggesting a promising approach for the design of potent dual COX-2/5-LO inhibitors.
ADVANCED THERAPEUTICS
(2023)
Article
Engineering, Biomedical
Yong Xu, Rebecca Rothe, Dagmar Voigt, Ahmed Sayed, Can Huang, Sandra Hauser, Pao-Wan Lee, Meiying Cui, James P. Saenz, Aldo R. Boccaccini, Kai Zheng, Jens Pietzsch, Yixin Zhang
Summary: By incorporating polyphosphate-modified hyaluronic acid and bioactive glass nano-fibril, we can create synthetic hydrogels that mimic the functions of extracellular matrix (ECM). These ECM-like hydrogels can be used for surface modification, 3D cell culture, and in vivo degradation. The system provides a versatile platform for investigating cell-biomatrix interactions.
ACTA BIOMATERIALIA
(2023)
Article
Biochemical Research Methods
Xuan Peng, Zeljko Janicijevic, Sandy Lemm, Markus Laube, Jens Pietzsch, Michael Bachmann, Larysa Baraban
Summary: The functional interaction between cancer cells and the surrounding microenvironment is not well understood, leading to the development of various in vitro tumor models. Factors such as nutrient transport, space availability, and confinement affect the size, shape, and metabolism of tumoroids. A low-cost method based on fluidics is presented to generate alginate and alginate-chitosan microcapsules for growing human hepatoma (HepG2) spheroids of different dimensions and geometries. The composition and thickness of the hydrogel shell are selectively tuned to control the permeability of the microcapsules. The diffusion of benchmark molecules through the shell is systematically investigated using experiments and simulations, ensuring efficient mass transfer and filtering of biochemical species. The metabolic activity of spheroids in microcapsules is confirmed through chromatography studies. Different phenotypic 3D cell assemblies are observed inside capsules based on available space, varying in cell aggregation tightness and shape. Overall, the system with tunable shell thickness and permeability provides a promising platform for studying cancer spheroid formation and their interaction with the surrounding microenvironment.
BIOTECHNOLOGY JOURNAL
(2023)
Article
Chemistry, Medicinal
Sebastian Braun, Svetlana Paskas, Markus Laube, Sven George, Bettina Hofmann, Peter Loennecke, Dieter Steinhilber, Jens Pietzsch, Sanja Mijatovic, Danijela Maksimovic-Ivanic, Evamarie Hey-Hawkins
Summary: The presence of inflammatory mediators in the tumor microenvironment indicates cancer-related inflammatory processes, and targeting these mediators and related signal pathways may provide a rational strategy for cancer treatment. This study focuses on incorporating carboranes into dual COX-2/5-LO inhibitors, key enzymes in eicosanoid biosynthesis. The results show that carborane-based tebufelone analogs exhibit no COX inhibition but 5-LO inhibitory activity, and structural modifications enhance their anticancer activity. Thus, this strategy is promising for designing potent 5-LO inhibitors with potential application as cytostatic agents.
Article
Nutrition & Dietetics
Rebecca J. J. Deyell, Sunil Desai, Andrea Gallivan, Alecia Lim, Michael B. B. Sawyer, Steven B. B. Heymsfield, Wei Shen, Vickie E. E. Baracos
Summary: This study established models to predict the whole-body skeletal muscle and fat composition in pediatric oncology patients using cross-sectional abdominal images, and analyzed a previously recruited cohort of healthy children using whole-body MRI, showing high correlation. The results indicate that cross-sectional area data can be used to predict the whole-body skeletal muscle and fat composition in pediatric patients.
EUROPEAN JOURNAL OF CLINICAL NUTRITION
(2023)
Article
Biochemistry & Molecular Biology
Franziska Striese, Christin Neuber, Sandy Graessel, Claudia Arndt, Martin Ullrich, Joerg Steinbach, Jens Pietzsch, Ralf Bergmann, Hans-Juergen Pietzsch, Wiebke Sihver, Marcus Frenz, Anja Feldmann, Michael P. Bachmann
Summary: Prostate specific membrane antigen (PSMA) is a promising target for imaging and treatment of prostate carcinoma (PCa), but alternative targets are needed. Prostate stem cell antigen (PSCA) is highly overexpressed in most PCa cells and correlates with tumor progression, making it a potential alternative target for theranostics. The radiolabeled antibody [Lu-177]Lu-CHX-A ''-DTPA-7F5 showed high tumor uptake and specificity in mice bearing PSCA-positive tumors, indicating its potential for imaging and radioimmunotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Oluwakemi Ebenezer, Pietro Comoglio, Gane Ka-Shu Wong, Jack A. Tuszynski
Summary: In the past two decades, the introduction of synthetic siRNAs into the cytoplasm has been found to effectively silence targeted genes, impacting gene expression and regulation. Extensive investments have been made in developing RNA therapeutics, including for diseases related to PCSK9. PCSK9 plays a crucial role in LDL-C uptake, and loss-of-function modifications of PCSK9 have shown significant clinical importance in reducing cholesterol levels and lowering the risk of CVD. Monoclonal antibodies and siRNA drugs targeting PCSK9 offer a promising option for managing lipid disorders and improving CVD outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Aarat P. Kalra, Somnath Biswas, Imani Mulrain, Michelle Wang, Jack A. Tuszynski, Gregory D. Scholes
Summary: Microtubules and actin filaments are protein polymers that have various energy conversion roles in cells. While their mechanochemical roles are well studied, their capabilities for photonic energy conversion are not well understood. This Perspective discusses the photophysical properties of protein polymers, the challenges and opportunities of integrating protein biochemistry with photophysics, and the potential of microtubules and actin filaments to serve as targets for photobiomodulation. It also presents the broad challenges and questions in the field of protein biophotonics, emphasizing the importance of understanding how protein polymers interact with light for biohybrid device fabrication and light-based therapeutics.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Martin Ullrich, Florian Brandt, Reik Loser, Jens Pietzsch, Robert Wodtke
Summary: The development of novel ligands for G-protein-coupled receptors (GPCRs) involves the characterization of their binding affinity, typically using radioligands in competition or saturation binding assays. GPCRs, being transmembrane proteins, require preparation of receptor samples from tissue sections, cell membranes, cell homogenates, or intact cells for binding assays. In this study, we characterized a series of Cu-64-labeled [Tyr(3)]octreotate (TATE) derivatives in vitro using saturation binding assays to investigate the binding parameters of the somatostatin receptor sub-type 2 (SST2) towards intact mouse pheochromocytoma cells and corresponding cell homogenates. We discuss the observed differences, considering the physiology of SST2 and GPCRs in general, and highlight the advantages and limitations of the methods used.
Article
Chemistry, Medicinal
Torsten Kniess, Joerg Zessin, Peter Maeding, Manuela Kuchar, Oliver Kiss, Klaus Kopka
Summary: This paper provides an overview of the radiosynthesis methods for [F-18]FMISO published so far. It discusses different precursors, radiolabeling approaches, purification methods, and automated radiosynthesizers used. The authors also report a GMP compliant radiosynthesis using original cassettes and an easy and efficient radiosynthesis using in-house prepared FASTlab cassettes.
EJNMMI RADIOPHARMACY AND CHEMISTRY
(2023)
Correction
Chemistry, Physical
Aarat P. Kalra, Somnath Biswas, Imani Mulrain, Michelle Wang, Jack A. Tuszynski, Gregory D. Scholes
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Review
Nutrition & Dietetics
Matthew T. J. Halma, Jack A. Tuszynski, Paul E. Marik
Summary: Cancer can be targeted metabolically through dietary and lifestyle changes, depriving cancer cells of glucose, and utilizing nutritional supplements and repurposed drugs, which can contribute to the prevention and treatment of cancer.
Article
Cell Biology
Anne Krueger-Genge, Susanne Koehler, Markus Laube, Vanessa Haileka, Sandy Lemm, Karolina Majchrzak, Sarah Kammerer, Christian Schulz, Joachim Storsberg, Jens Pietzsch, Jan-Heiner Kuepper, Friedrich Jung
Summary: Cancer patients have a high risk of thrombotic events, possibly due to tumor cell detachment or the effects of chemotherapeutic agents. Cyclophosphamide (CPA) is a commonly used drug that requires activation by cytochrome P450 enzymes (CYP). We hypothesize that CPA could induce thrombosis by damaging endothelial cells (EC) through metabolization or direct damage. In our study, HUVECs were treated with CPA and showed DNA damage, reduced EC layer formation, and increased release of prothrombotic substances. This suggests that CPA treatment may contribute to the risk of thrombus formation.
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)
