Article
Pharmacology & Pharmacy
Cai Read, Duuamene Nyimanu, Peiran Yang, Rhoda E. Kuc, Thomas L. Williams, Christopher M. Fitzpatrick, Richard Foster, Robert C. Glen, Janet J. Maguire, Anthony P. Davenport
Summary: CMF-019, a small molecule apelin agonist, demonstrates strong vasodilatory effects in vivo and protects human pulmonary artery endothelial cells from apoptosis. It exhibits remarkable bias at the apelin receptor and could serve as the basis for designing novel therapeutic agents for chronic diseases.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Kohei Umedera, Taiki Morita, Atsushi Yoshimori, Kentaro Yamada, Akira Katoh, Hiroyuki Kouji, Hiroyuki Nakamura
Summary: A novel sp(3) carbon-rich tricyclic 3D scaffold-based peptide mimetic compound library was constructed to target protein-protein interactions. The designed compounds exhibited potential antiproliferative, anti-cancer, and antiviral activities, with compound 21a showing the strongest inhibitory activity against HIF-1 transcriptional activity.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Review
Chemistry, Medicinal
Aizhan Abdildinova, Mark J. Kurth, Young-Dae Gong
Summary: Peptidomimetics are a unique class of drug molecules, and solid-phase synthesis is an important tool for synthesizing these molecules, where small molecules including heterocycles play a key role as drug cores.
Article
Pharmacology & Pharmacy
Yunlu Jiang, Maocai Yan, Chunmei Wang, Qinqin Wang, Xiaoyu Chen, Rumin Zhang, Lei Wan, Bingyuan Ji, Bo Dong, Huiyun Wang, Jing Chen
Summary: Research showed that different Apelin and Elabela ligands activated APJ resulted in distinct G protein-dependent and beta-arrestin-dependent signaling pathways. Elabela-32 exhibited a >1000-fold bias towards the beta-arrestin-dependent pathway, while Apelin-17 was biased towards the beta-arrestin-dependent signaling. Eabela-21 and pGlu(1)-Apelin-13 showed very different activities on the G protein-dependent pathway.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Chemistry, Multidisciplinary
Anuradha Mehra, Rekha Sangwan
Summary: Benzimidazole derivatives, discovered in the late 19th and early 20th centuries, have played a pivotal role in pharmacology and have had a profound impact on medicine and healthcare. These compounds have exhibited diverse pharmacological properties, including potent anticancer activity and potential as antihypertensive and antidiabetic agents. Structural modifications have been explored to expand the range of effective drugs. The expanding potential of benzimidazole derivatives in treating various diseases is summarized in this review.
Article
Biochemistry & Molecular Biology
Sanju Narayanan, Donghua Dai, Ravi Kumar Vyas Devambatla, Vincent Albert, Nicolas Bruneau-Latour, Vineetha Vasukuttan, Stephane Ciblat, Kenneth Rehder, Scott P. Runyon, Rangan Maitra
Summary: A potent and selective APJ agonist suitable for studying APJ activity in peripheral tissues after oral administration has been developed.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Endocrinology & Metabolism
Borhan Shokrollahi, Hai-Ying Zheng, Ling-Yu Li, Li-Ping Tang, Xiao-Ya Ma, Xing-Rong Lu, An-Qin Duan, Yu Zhang, Xiao-Hui Tan, Chen-Xi Huang, Yuan-Yuan Xu, Jiang-Hua Shang
Summary: This study investigated the expression levels of APLN/APJ in buffalo ovarian granulose cells (GCs) and the effects of IGF1 and FSH on APLN/APJ expression. The results showed that APLN expression was highest in large-sized GCs, while APJ expression increased with follicle enlargement. IGF1 and FSH increased the expression of APLN and FSH, and IGF1 also increased the expression of APJ. Both isoforms of APLN increased the secretion of E2 and P4, potentially through upregulation of CYP19A1 and StAR expression. In conclusion, APLN may play a crucial role in steroidogenesis and follicular development in buffalo ovarian GCs.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Prafullya Kumar Mudi, Ayan Kumar Mahanty, Muddukrishnaiah Kotakonda, Sunnapu Prasad, Subires Bhattacharyya, Bhaskar Biswas
Summary: The manuscript describes the green-chemical synthesis of a new diindole-substituted benzimidazole compound, B1, and investigates its screening activity against SARS-CoV-2. The results demonstrate that B1 exhibits high activity and inhibition against the virus, with strong interactions observed with the main protease and non-structural proteins of SARS-CoV-2. These findings suggest that the synthetic benzimidazole scaffold has potential inhibitory properties against SARS-CoV-2.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Medicine, Research & Experimental
Jing Chen, Zhengwen Wang, Rumin Zhang, Haiyan Yin, Peixiang Wang, Chunmei Wang, Yunlu Jiang
Summary: The study reveals the formation of a heterodimer between APJ and ORL1, which play roles in signaling and physiological effects. The APJ-ORL1 dimer exhibits a biased signaling pathway that is G protein-dependent. The structural interface of the dimer switches from TM1/TM2 to TM5 upon activation.
Article
Medicine, General & Internal
J. Park, M-Y Park, Y. Kim, Y. Jun, U. Lee, C-M Oh
Summary: This study found that [Pyr1]-Apelin-13 can protect cells from viral infection by inhibiting the binding of ACE2 to the SARS-CoV-2 spike protein. It also regulates inflammatory responses by inhibiting the nuclear factor kappa B pathway. These findings suggest that Apelin may be a potential therapeutic candidate against SARS-CoV-2 infection.
QJM-AN INTERNATIONAL JOURNAL OF MEDICINE
(2023)
Article
Polymer Science
Sarah N. Hancock, Nattawut Yuntawattana, Sara M. Valdez, Quentin Michaudel
Summary: Pyridine-containing polymers have great potential in various applications, but the innate Lewis basicity hampers living polymerization catalyzed by transition-metal complexes. In this study, well-controlled chain-growth ring-opening metathesis polymerization was achieved by careful structural design of pyridinonorbornene monomers. Polypyridinonorbornenes exhibited high T-g and T-d, which is promising for high-temperature applications. Investigation of the polymerization kinetics and reactivity of the chain ends revealed the influence of nitrogen coordination on the chain-growth mechanism.
Article
Chemistry, Physical
P. U. Ashvin Iresh Fernando, Gilbert K. Kosgei, Timothy Schutt, Glen Jenness, Chun-Hsing Chen, Garrett W. George, Ashley N. Kimble, William M. Nelson, David L. Henderson, Lee C. Moores
Summary: Functionalized molecular design enables selective binding and signaling of perchlorate ions in aqueous solutions. Pyrene-benzimidazole-based bipodal molecular scaffolds were investigated for their response to perchlorate detection in acid-buffered media. These molecules exhibit a significant and selective turn-on response to perchlorate ions, even in the presence of heavy metal ions. The molecule's structure and characteristics were determined through various methods, including NMR, X-ray crystallography, computational modeling, absorption spectroscopy, and fluorescence spectroscopy. Additionally, the molecule is sensitive to changes in pH, making it useful for detecting local environmental changes.
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Animesh Roy, Eric Koesema, Thomas Kodadek
Summary: A powerful quality control method has been developed to distinguish efficiently cyclizing scaffolds during solid-phase synthesis of thioether macrocycles without the need for tedious liquid chromatography/mass spectrometry analysis. This method can also identify linear impurities in a DNA-encoded library of macrocycles and establish a useful quality control protocol for re-synthesis of putative macrocyclic screening hits.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Physiology
Gonghui Hu, Zhen Wang, Rumin Zhang, Wenping Sun, Xiaoyu Chen
Summary: The apelin/APJ system plays crucial roles in various physiological and pathological functions, such as fluid homeostasis, cardiovascular and metabolic disorders. In addition to forming a complex with its ligand and associated G proteins, APJ may interact with other GPCRs to selectively modulate different signal transduction pathways. Further research on the metabolism and signaling pathways associated with the apelin/APJ system is necessary to provide more precise guidance for the development of clinical drugs.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Chemistry, Physical
Maheshwerreddy Chilamari, Jacob R. Immel, Pei-Hsuan Chen, Bayan M. Alghafli, Steven Bloom
Summary: By combining a biocompatible flavin photocatalyst with a palladium catalyst, the study achieved the construction of isotopically enriched peptidomimetics and other synthetic reactions in water. The ligand and palladium oxidation state played crucial roles in controlling product selectivity during synthetic peptide construction.
Article
Multidisciplinary Sciences
Nirit Lev, Yael Barhum, Tali Ben-Zur, Israel Aharony, Lena Trifonov, Noa Regev, Eldad Melamed, Arie Gruzman, Daniel Offen
Article
Chemistry, Medicinal
Lena Trifonov, Vadim Nudelman, Michael Zhenin, Erez Matsree, Michal Afri, Bruria Schmerling, Guy Cohen, Krzysztof Jozwiak, Michal Weitman, Edward Korshin, Hanoch Senderowitz, Asher Shainberg, Edith Hochhauser, Arie Gruzman
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Chemistry, Organic
Lena Trifonov, Ayelet Rothstein, Edward E. Korshin, Olga Viskind, Michal Afri, Gregory Leitus, Krzysztof Palczewski, Arie Gruzman
Summary: Here, a simplified synthesis of rarely explored alkylidene cyclopent-2-en-4-ones was achieved through an uncommon olefination reaction. A plausible mechanism for these transformations was proposed. Analysis using single crystal X-ray diffraction and NMR spectroscopy revealed that the products exist as two diastereomers.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Lena Trifonov, Katerina Chumin, Raanan Gvirtz, Michal Afri, Edward E. Korshin, Guy Cohen, Arie Gruzman
MENDELEEV COMMUNICATIONS
(2020)