Article
Chemistry, Medicinal
Tony Ge, Jean-Christophe Cintrat
Summary: Heterocyclic amino derivatives have proven to be potent bioactive compounds, with novel heterocycles showing promise as building blocks in drug discovery. Pyrrolotriazinones, in particular, have attracted attention for their potential biological activities.
Article
Biochemistry & Molecular Biology
Tjasa Gorican, Luka Ciber, Nejc Petek, Jurij Svete, Marko Novinec
Summary: Cathepsins K and S are closely related papain-like cysteine peptidases, potential therapeutic targets for metabolic and inflammatory diseases. In this study, a new hyperbolic inhibitor of cathepsin K and the potential of succinimide scaffold as inhibitors of cathepsins K and S were investigated. Small molecules hyperbolic inhibitors of cathepsin S were identified, which will be further explored for potential inhibition of cysteine cathepsins in in vitro models.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Huifang Shan, Xinyu Ma, Guoyi Yan, Meng Luo, Xinxin Zhong, Suke Lan, Jie Yang, Yuanyuan Liu, Chunlan Pu, Yu Tong, Rui Li
Summary: A series of covalent CDK4/6 inhibitors were designed and synthesized, with compound C-13 showing potent anticancer activity in vitro and significant tumor growth inhibition in a mouse model.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Zhibo Luo, Lingli Wang, Zhifei Fu, Bin Shuai, Miaorong Luo, Guoping Hu, Jian Chen, Jikui Sun, Jiansong Wang, Jian Li, Shuhui Chen, Yang Zhang
Summary: The researchers designed and synthesized a series of novel RET inhibitors based on BLU-667 structure, with compound 9 identified as a potent selective RET inhibitor showing improved drug-like properties. Compound 9 exhibited good inhibitory effects on mutant RET and effectively suppressed the proliferation of cells transfected with KIF5B-RET fusion gene. It also displayed fewer 'off-target' effects compared to BLU-667, making it a promising lead for discovering RET-directed therapeutic agents.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Agronomy
Hao Huang, Jian-qiu Zhang, Jian-min Liu, Man-man Wang, Lei Shu, Yi-le Yan, Xiao-hang Zhan, Ping Wang, Xue-ting Huan, Da-yong Zhang
Summary: The study synthesized a series of compounds for herbicidal experiments, with B14 and B18 displaying excellent herbicidal activity and potential for weed control in maize fields. The results suggest that the pyrazole-benzofuran structure could be used as lead compounds for the development of HPPD inhibitors.
PEST MANAGEMENT SCIENCE
(2021)
Article
Chemistry, Medicinal
Valentin Duvauchelle, Patrick Meffre, Zohra Benfodda
Summary: 2-Aminothiophene is an attractive core structure that exhibits broad biological activities and serves as a precursor for the synthesis of active thiophene-containing compounds. Compounds derived from 2-aminothiophene are promising in medicinal chemistry as selective inhibitors and modulators, showing effective pharmacological properties in clinical studies of specific diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Karina Margareti Alencar de Barros, Janaina de Cassia Orlandi Sardi, Simone Maria-Neto, Alexandre Jose Macedo, Suellen Rodrigues Ramalho, Daniella Gorete Lourenco de Oliveira, Gemilson Soares Pontes, Simone Schneider Weber, Caio Fernando Ramalho de Oliveira, Maria Ligia Rodrigues Macedo
Summary: The study characterized a new Kunitz-type inhibitor EpTI from E. poeppigiana seeds, showing antimicrobial, anti-adhesion, and anti-biofilm properties against both Grampositive and negative bacteria. The inhibitor demonstrated low toxicity in an animal model and could potentially be used to design novel drug prototypes.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Chemistry, Medicinal
Yang Yang, Xin Sun, Leixuan Luo, Rujue Peng, Ruiqing Yang, Zhenjie Cheng, Yao Lv, Hongfeng Li, Qidong Tang, Wufu Zhu, Dan Qiao, Shan Xu
Summary: In this study, a novel class of PI3K/mTOR dual inhibitors was developed through scaffold hopping and synthesis, with compound Y-2 showing promising inhibitory effects. Pharmacological experiments confirmed the antitumor activity of Y-2, and its inhibitory effect on mTOR kinase was significantly greater than that of the reference drug GDC-0941. The study provides a valuable candidate for cancer treatment.
ARCHIV DER PHARMAZIE
(2023)
Article
Chemistry, Medicinal
Xin Li, Ping Dong, Ting Zhang, Guodong Cai, Yang Chen, Huaide Dong, Fang Yang, Lei Zhang, Yuchang Mao, Jun Feng, Chang Bai, Feng He, Weikang Tao
Summary: In this study, we designed and synthesized a novel scaffold featuring a pyrrole-fused urea template. The lead compound, SHR2415, exhibited high cell potency in the Colo205 assay and favorable PK profiles across species. Furthermore, SHR2415 showed robust in vivo efficacy in a mouse Colo205 xenograft model.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Haibo Lu, Tian Lu, Shijia Zu, Zhe Duan, Yiman Guang, Qi Li, Jingyi Ma, Dongying Chen, Bo Li, Wenchao Lu, Hualiang Jiang, Cheng Luo, Deyong Ye, Kaixian Chen, Hua Lin
Summary: This study reports the discovery of a series of CECR2 BRD inhibitors and identifies DC-CBi-22 as the most potent compound. DC-CBi-22 exhibits strong inhibitory activity against CECR2 BRD and shows selectivity over BPTF BRD. This finding is important for the study of CECR2.
BIOORGANIC CHEMISTRY
(2022)
Editorial Material
Biology
Tathagata Biswas, Jaya Krishnan, Nicolas Rohner
Summary: Comparing the genomes of mammals with poor vision has identified a key gene related to eyesight.
Review
Chemistry, Medicinal
Mohammad Abrar Alam
Summary: Pyrazole derivatives have shown promising potential in the treatment of various diseases and have been widely used in approved drugs. The number of drugs containing pyrazole nucleus has significantly increased in recent years, with successful applications in cancer treatment, HIV therapy, and other areas.
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Aida Buza, Cuneyt Turkes, Mustafa Arslan, Yeliz Demir, Busra Dincer, Arleta Rifati Nixha, Sukru Beydemir
Summary: Sulfonamides bearing 1,2,3-triazole moiety were designed as inhibitors of human alpha-carbonic anhydrases (hCAs). Some derivatives showed selectivity towards the hCA I and II isoforms. The synthesized compounds demonstrated significant antiproliferative activity and minimal cytotoxicity in various cell lines.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Medicinal
Giulia Bononi, Miriana Di Stefano, Giulio Poli, Gabriella Ortore, Philip Meier, Francesca Masetto, Isabella Caligiuri, Flavio Rizzolio, Marco Macchia, Andrea Chicca, Amir Avan, Elisa Giovannetti, Chiara Vagaggini, Annalaura Brai, Elena Dreassi, Massimo Valoti, Filippo Minutolo, Carlotta Granchi, Juerg Gertsch, Tiziano Tuccinardi
Summary: The study reveals the potential of benzylpiperidine-based MAGL inhibitors in pancreatic cancer treatment. Inhibition of MAGL can reduce cell migration and promote apoptosis, synergizing with chemotherapy drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Agriculture, Multidisciplinary
Yu-Hao Zhang, Shan-Shan Yang, Qi Zhang, Tian-Tian Zhang, Tian-Yi Zhang, Bo-Hang Zhou, Le Zhou
Summary: Based on the structural features of succinate dehydrogenase inhibitors (SDHIs) and targeted covalent inhibitors, N-phenylpropiolamides with a Michael acceptor moiety were designed to find new antifungal compounds. Nineteen compounds demonstrated potent inhibition activity on nine plant pathogenic fungi. Compound 13 showed complete inhibition of Physalospora piricola infection on apples at a concentration of 200 μg/mL over 7 days and exhibited high safety to plant germination and seedling growth. It was identified as an SDH inhibitor with comparable activity to the positive drug boscalid.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Chemistry, Applied
Yedukondalu Nalli, Suraya Jan, Gianluigi Lauro, Javeed Ur Rasool, Waseem I. Lone, Aminur R. Sarkar, Junaid Banday, Giuseppe Bifulco, Hartmut Laatsch, Sajad H. Syed, Asif Ali
Summary: In this study, the isolation, synthesis, and structure determination of cannabidiol and its derivatives were reported, along with their cytotoxic activities against eight cancer cell lines. Compounds 4, 5, 7, and 8 showed significant in vitro cytotoxic activity, with compounds 4 and 7 being comparable to the parent molecule 1 in inhibiting the tested cancer cell lines.
NATURAL PRODUCT RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Nanqing Zhou, Jessica L. Keffer, Shawn W. Polson, Clara S. Chan
Summary: This study explored the physiology and gene expression of a facultative Fe(II)-oxidizing bacterium, revealing a direct connection between Fe(II) oxidation and carbon fixation.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Dafne Ruggiero, Stefania Terracciano, Gianluigi Lauro, Michela Pecoraro, Silvia Franceschelli, Giuseppe Bifulco, Ines Bruno
Summary: The BAG3 protein is involved in multiple cellular pathways and its elevated expression in tumor cells promotes cell survival and apoptosis resistance. It has been identified as a potential target for controlling cancer-related signaling pathways. A synthetic BAG3 modulator, compound 6, has been discovered with significant anti-proliferative effects on cancer cells.
Article
Plant Sciences
Milena Masullo, Gianluigi Lauro, Antonietta Cerulli, Giuseppe Bifulco, Sonia Piacente
Summary: This study evaluated the inhibitory effects of diarylheptanoids from C. avellana byproducts on alpha-glucosidase enzyme and elucidated their inhibitory mechanism through molecular docking experiments. LC-MS analysis revealed the presence of giffonin J, K, and P in C. avellana byproducts, particularly in the ethanol extract of the leaves. These findings suggest that C. avellana byproducts, especially the leaves, could serve as a prospective source of bioactive diarylheptanoids for the development of functional ingredients for diabetes treatment.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Anella Saviano, Simona De Vita, Maria Giovanna Chini, Noemi Marigliano, Gianluigi Lauro, Gian Marco Casillo, Federica Raucci, Maria Iorizzi, Robert Klaus Hofstetter, Katrin Fischer, Andreas Koeberle, Oliver Werz, Francesco Maione, Giuseppe Bifulco
Summary: Tanshinone IIA (TIIA) and cryptotanshinone (CRY) were found to inhibit the COX-2/mPGES-1/EP3 pathway, suggesting their potential as anti-inflammatory and anti-thrombotic agents.
Article
Biochemistry & Molecular Biology
Jiadong Sun, Gengxiang Zhao, Tatsiana Bylund, Myungjin Lee, Srikar Adibhatla, Peter D. Kwong, Gwo-Yu Chuang, Reda Rawi, Carole A. Bewley
Summary: Lectins, such as the therapeutic lectin griffithsin (GRFT), have the potential to bind to carbohydrates and glycan shields, making them promising for therapeutic and diagnostic applications. By studying the structure and activity of GRFT, researchers have identified a critical core structure that is important for antiviral activity and binding to high mannose glycans. This discovery may help in designing carbohydrate receptors and improving the affinity and stability of known lectins.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biology
Kira S. Makarova, Brittney Blackburne, Yuri Wolf, Anastasia Nikolskaya, Svetlana Karamycheva, Marlene Espinoza, Clifton E. Barry, Carole A. Bewley, Eugene Koonin
Summary: This study comprehensively analyzed BGCs encoding graspetides and reported several novel graspetide groups and associated proteins involved in their biosynthesis and expression. The results revealed previously unsuspected diversity in graspetide sequences and expanded the known diversity of RiPPs. The findings of this study are important for advancing approaches to identify RiPPs.
Article
Integrative & Complementary Medicine
Isabel Urena-Vacas, Elena Gonzalez-Burgos, Simona De Vita, Padreep K. Divakar, Giuseppe Bifulco, M. Pilar Gomez-Serranillos
Summary: This study evaluated the antioxidant capacity and enzyme inhibitory activities of 14 lichen extracts belonging to the cetrarioid clade. The results showed that certain lichens exhibited strong antioxidant capacity and enzyme inhibitory activities, suggesting their potential use in the treatment of neurodegenerative diseases. The study also identified several promising secondary metabolites in these lichen extracts.
EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
(2022)
Article
Plant Sciences
Sihem Boudermine, Valentina Parisi, Redouane Lemoui, Tarek Boudiar, Maria Giovanna Chini, Silvia Franceschelli, Michela Pecoraro, Maria Pacale, Giuseppe Bifulco, Alessandra Braca, Nunziatina De Tommasi, Marinella De Leo
Summary: Seven new terpenoids, along with eight known compounds, were isolated from Ammoides atlantica. Compounds 8 and 10 displayed significant dose-dependent reduction in cell viability and exhibited potential apoptotic and cell cycle inhibition effects.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Chemistry, Organic
Ester Colarusso, Erica Gazzillo, Eleonora Boccia, Assunta Giordano, Maria Giovanna Chini, Giuseppe Bifulco, Gianluigi Lauro
Summary: Novel 6-methylquinazolin-4(3H)-one-based compounds were identified and synthesized as binders of the BRD9 epigenetic reader. Molecular docking experiments led to the selection of 16 compounds with good yields and binding potency toward BRD9, with compounds 14, 16, 18, 22, and 26 showing the highest activity.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Plant Sciences
Giuliana Donadio, Maria Giovanna Chini, Valentina Parisi, Francesca Mensitieri, Nicola Malafronte, Giuseppe Bifulco, Angela Bisio, Nunziatina De Tommasi, Ammar Bader
Summary: Sixteen diterpenes, along with 10 previously described compounds, were isolated from Psiadia punctulata in Saudi Arabia. The diterpene structures were determined using NMR spectroscopy and mass spectrometry data. One of the compounds, psiadin, showed synergistic effect with the antiseptic chlorhexidine and potential inhibition activity against bacterial efflux pumps.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Chemistry, Medicinal
Simone Di Micco, Gianluigi Lauro, Giuseppe Bifulco
Summary: This study used molecular dynamics simulations to investigate the structure and function of microsomal prostaglandin E-2 synthase-1 (mPGES-1) protein systems. The results revealed the structural role of glutathione (GSH) in the enzyme's chemical architecture and confirmed the stability of the enzyme machinery. The analysis also showed the involvement of residue R73 in solvent exchange events and suggested that it does not serve as a channel for GSH entry into the endoplasmic reticulum membrane.
MOLECULAR INFORMATICS
(2022)
Review
Chemistry, Multidisciplinary
Carole A. Bewley, Gary A. Sulikowski, Zhongyue J. Yang, Giuseppe Bifulco, Hyo-Moon Cho, Christopher R. Fullenkamp
Summary: Natural products, produced by enzymatic assembly lines, have played a crucial role in the discovery of antibiotics, antineoplastics, and therapeutics. They have unique three-dimensional shapes and stereochemistry, which determine their diverse functions and biological activities. With advancements in methods and tools, research on atropisomerism in natural products and related scaffolds is progressing.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Plant Sciences
Federica Rogati, Chiara Maioli, Gianluigi Lauro, Diego Caprioglio, Daniela Imperio, Erika Del Grosso, Bruno Botta, Luisa Mannina, Giuseppe Bifulco, Cinzia Ingallina, Alberto Minassi
Summary: In this study, a vintage photochemical approach was used to discover an unexpected reactivity pathway related to Delta 1-3-oxo-pentacyclic triterpenic acids, leading to a new class of natural-unnatural 5(10 -> 1)abeo-pentacyclic triterpenic acids.
JOURNAL OF NATURAL PRODUCTS
(2023)