Article
Biochemistry & Molecular Biology
Carmine Marco Morgillo, Antonio Lupia, Alessandro Deplano, Luciano Pirone, Bianca Fiorillo, Emilia Pedone, F. Javier Luque, Valentina Onnis, Federica Moraca, Bruno Catalanotti
Summary: FAAH is a key enzyme in controlling cannabinoid signaling, and research on the mechanism of action of the non-competitive inhibitor TPA14 has provided a theoretical basis for the design of effective drugs for the treatment of neuropathic pain and chronic inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Chemistry, Multidisciplinary
Yuwei Sheng, Meijuan Zhou, Changjun You, Xiaoxia Dai
Summary: DNA methylation is a key type of DNA modification that plays important roles in biological processes. Recent studies have identified N-6-methyladenine (6mA) as an internal DNA modification that occurs dynamically in various eukaryotes, including humans. Increasing evidence suggests that 6mA may act as a novel epigenetic modification involved in the regulation of development, stress response, and diseases such as cancer and neurodegenerative disorders. This review summarizes the recent advances in detecting and studying the functional effects of 6mA modification, focusing on its biological consequences, relevance to human health, and dynamic regulation by methyltransferases, demethylases, and 6mA-binding proteins. Further research on the chemical and biological aspects of 6mA modification is expected to provide a better understanding of its potentially important roles in normal and pathological biological processes.
CHINESE CHEMICAL LETTERS
(2022)
Article
Chemistry, Medicinal
Marco Daniele Parenti, Marina Naldi, Elisabetta Manoni, Edoardo Fabini, Daniela Cederfelt, Vladimir O. Talibov, Valeria Gressani, Ummu Guven, Valentina Grossi, Candida Fasano, Paola Sanese, Katia De Marco, Alexander A. Shtil, Alexander V. Kurkin, Andrea Altieri, U. Helena Danielson, Giuseppina Caretti, Cristiano Simone, Greta Varchi, Manuela Bartolini, Alberto Del Rio
Summary: Recent findings suggest that inhibiting SMYD3 methyltransferase could be a therapeutic strategy for certain deadly cancer types. This study designed active site-selective covalent SMYD3 inhibitors and demonstrated their ability to attenuate tumor biology at the cellular and genetic levels, inhibiting important genes and cell proliferation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Shelby C. Yuhas, Ananya Majumdar, Marc M. Greenberg
Summary: Covalent inhibitors 1 and 9 have been found to effectively inhibit the polymerase and lyase activities of Pol beta by preventing DNA binding. These inhibitors could serve as useful tools for studying the role of wild type and mutant forms of Pol beta and other polymerases in DNA repair.
Article
Chemistry, Medicinal
Yi Zhang, Deqin Rong, Bingbing Li, Yuanxiang Wang
Summary: Epigenetic regulation is crucial in physiological processes, with dysregulation linked to diseases like cancer. Covalent small-molecule inhibitors show promise in enhancing selectivity and efficacy, but face challenges.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Immunology
Shao-Chen Yang, Wu-Yin Wang, Jun-Jie Zhou, Lei Wu, Meng-Jie Zhang, Qi-Chao Yang, Wei-Wei Deng, Zhi-Jun Sun
Summary: DNMT1 is highly expressed in oral squamous cell carcinoma (OSCC) and is associated with poor prognosis. DNMT1 inhibitors can improve the tumor microenvironment and delay tumor growth.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Review
Genetics & Heredity
Niels H. Gehring, Jean-Yves Roignant
Summary: Splicing of precursor mRNAs is essential for eukaryotic gene expression, with accurate identification of splice sites and intron removal being crucial for producing desired mRNA isoforms. Recent research has uncovered noncanonical splicing mechanisms that play key roles in gene expression regulation, in addition to well-understood basic splicing regulation mechanisms.
TRENDS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Irina R. Arkhipova, Irina A. Yushenova, Fernando Rodriguez
Summary: DNA methylation is a prominent feature of epigenetics, with DNA methyltransferases being transferred from prokaryotes to eukaryotes and co-opted into epigenetic regulatory systems. While the role of C5-methylcytosine in epigenetics is well-studied, the epigenetic effects of other methylated bases are less understood. The discovery of N4-methylcytosine of bacterial origin in metazoan DNA challenges the existing paradigms of eukaryotic regulatory systems' origin and evolution.
Article
Chemistry, Multidisciplinary
Yudai Tabuchi, Jay Yang, Masumi Taki
Summary: This study created a DNA-aptamer-type covalent drug which can be deactivated and reactivated through a specific structure, providing a new approach to alleviate irreversible adverse drug effects.
CHEMICAL COMMUNICATIONS
(2021)
Article
Cell Biology
Claus Desler, Jon Ambaek Durhuus, Thomas Lau-Lindestrand Hansen, Sharath Anugula, Nadia Thaulov Zelander, Sisse Boggild, Lene Juel Rasmussen
Summary: The correlation between mitochondrial function and oncogenesis is complex and not fully understood. This study demonstrates that inhibition of mitochondrial-linked pyrimidine synthesis in cancer cells results in a more aggressive tumor phenotype, without affecting DNA repair ability.
Article
Oncology
Ramesh Elango, Radhakrishnan Vishnubalaji, Hibah Shaath, Nehad M. Alajez
Summary: Our study revealed the transcriptome alterations in TNBC in response to DNMT inhibition, including inhibition of cell proliferation, induction of cell death, and activation of specific gene networks.
CANCER CELL INTERNATIONAL
(2021)
Article
Chemistry, Multidisciplinary
Changqing Wu, Yu'e Liu, Wenju Liu, Tianhui Zou, Shaojuan Lu, Chengjie Zhu, Le He, Jie Chen, Lan Fang, Lin Zou, Ping Wang, Lihong Fan, Hongxiang Wang, Han You, Juxiang Chen, Jing-Yuan Fang, Cizhong Jiang, Yufeng Shi
Summary: This study identified the NNMT-DNMT1 axis as a critical molecular mechanism determining cancer cell sensitivity to OXPHOS inhibition, and revealed NNMT and DNMT1 as reliable biomarkers for OXPHOS-targeting cancer therapies.
Article
Pharmacology & Pharmacy
Maan T. Khayat, Abdelsattar M. Omar, Farid Ahmed, Mohammad I. Khan, Sara M. Ibrahim, Yosra A. Muhammad, Azizah M. Malebari, Thikryat Neamatallah, Moustafa E. El-Araby
Summary: This study investigated the structural-activity relationships (SARs) of tirbanibulin, a dual Src kinase/tubulin inhibitor. The newly synthesized compounds showed promising anticancer activity, with the most potent compound demonstrating cytotoxic effects against colon cancer and leukemia cell lines. Mechanistic studies revealed that this compound downregulates several kinases and suppresses specific signaling pathways, suggesting its potential as a lead compound for anticancer drug development.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Physical
Nadeem Abad, Lelfia Guelmami, Amel Haouas, Melek Hajji, Mohamed El Hafi, Jihad Sebhaoui, Taha Guerfel, Joel T. Mague, El Mokhtar Essassi, Youssef Ramli
Summary: This contribution presents the synthesis and structural characterization of a new quinoxaline derivative, 1-pentyl-3-phenylquinoxalin-2(1H)-one. The solid-state framework of the compound is governed by pi-stacking, C-H...O/pi hydrogen bonding, C--O...pi interactions, and C-H...H-C dispersive contacts. Computational tools are used to analyze the non-covalent interactions and gain insights into the chemical reactivity of the compound at both global and local levels.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Multidisciplinary
Hesheng Wang, Siyu Li, Yue Cui, Minqiang Liu, Xiubin Bu, Hua Tian, Xiaobo Yang
Summary: In this study, a visible-light-induced three-component cascade reaction was successfully achieved using a two-dimensional imine-linked covalent organic framework (2D-COF-5) as the heterogeneous photocatalyst. The reaction proceeded selectively, environmentally friendly, and sustainably, leading to the synthesis of various C3 trifluoroalkyl and trifluoroalkenyl quinoxalin-2(1H)-one derivatives with high yields. The reusability of 2D-COF-5 was also investigated and showed good maintenance of photocatalytic performance, chemical structure, and appearance in eight recycling runs.
NEW JOURNAL OF CHEMISTRY
(2022)