Article
Chemistry, Multidisciplinary
Alice Kennett, Sven Epple, Gabriella van der Valk, Irene Georgiou, Evelyne Gout, Romain R. Vives, Angela J. Russell
Summary: This study presents the design and synthesis of sulfated disaccharide inhibitors based on IdoA(2S)-GlcNS(6S), which showed potent inhibition of Sulf-2. The results suggest that IdoA(2S)-GlcNS(6S) is the shortest fragment size required for effective inhibition of Sulfs, and a trisulfated disaccharide is identified as the minimal fragment size of heparan sulfate for effective endosulfatase inhibition.
CHEMICAL COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Jia Xu, Xue Li, Xing-Yu Chen, Yu-Ting He, Jie Lei, Zhong-Zhu Chen, Zhi-Gang Xu
Summary: a-Ketoamide moieties can be used as privileged units to develop compounds with favorable biological activities, such as low toxicity, promising PK and drug-like properties. An efficient silver-catalyzed decarboxylative acylation was developed to derivatize the a-ketoamide functional group via a multicomponent reaction cascade sequence in one pot. A series of a-ketoamides were synthesized with three components, isocyanides, aromatic a-oxocarboxylic acid analogues, and water, in moderate yields. The research confirmed that the oxygen atom of the amide moiety was derived from water and air as the sole oxidant for the whole process.
Article
Chemistry, Organic
Marta Lubos, Lucie Mrazkova, Petra Gwozdiakova, Jan Picha, Milos Budesinsky, Jiri Jiracek, Jakub Kaminsky, Lenka Zakova
Summary: This study describes the synthesis, structures, and biological activities of six shortened analogues of human preptin. Stapled peptides with stabilized secondary structures were created by modifying the C-terminal part of preptin. The effect of these structural changes on calcium ion release was determined, and one of the analogues showed similar potency to the full-length preptin. These findings suggest the potential for designing new preptin analogues for diabetes and osteoporosis treatment.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Organic
Zhe Luo, Changtong Lu, Gary Histand, Dongen Lin
Summary: A cross-dehydrogenation coupling reaction between purines and alcohols, induced by visible light, using an acridinium photocatalyst and air as the sole oxidant, has been developed to synthesize a series of C8-alkoxy purine derivatives. This protocol offers a green and novel approach to construct the C-8-O bond on a purine ring with high step and atom economy.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
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
Yuhan Zhao, Xia Meng, Changqun Cai, Lingyun Wang, Hang Gong
Summary: In this work, a catalyst-, transition metal-, oxidant-free strategy was developed for the synthesis of alpha-ketoamides via an electrochemical decarboxylative acylation of isocyanides at room temperature with carbon dioxide as a sole by-product. This strategy is simple, rapid, and practical, and allows for the synthesis of highly functionalized alpha-ketoamides with high atom economy.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Chong Huang, Rui Zeng, Jingxin Qiao, Baoxue Quan, Ronghua Luo, Qiao Huang, Nihong Guo, Yueyue Li, Xinyan Long, Ronggang Ma, Anjie Xia, Zhen Fang, Yifei Wang, Yueshan Li, Yongtang Zheng, Linli Li, Jian Lei, Shengyong Yang
Summary: Researchers have discovered a series of α-ketoamide derivatives as a new class of SARS-CoV-2 M-pro inhibitors. One of these compounds showed high inhibitory activity and exhibited favorable pharmacokinetic properties. It displayed high target specificity for M-pro against human proteases and low toxicity, making it a potential lead compound for drug discovery.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Yusuke Tokuhiro, Kosuke Yoshikawa, Sei Murayama, Takeshi Nanjo, Yoshiji Takemoto
Summary: This article presents an alternative practical method for the asymmetric synthesis of beta-amino-alpha-ketoacid equivalents, utilizing a highly stereoselective organocatalyzed Mannich-type addition using glyoxylate cyanohydrin. The optimal aminothiourea catalyst provides a variety of adducts with excellent yield and stereoselectivity, and the reaction can be applied to a wider range of imine precursors. Experimental and computational studies reveal the factors contributing to the high diastereoselectivity and enantioselectivity of the reaction.
Article
Biochemistry & Molecular Biology
Nishad Thamban Chandrika, Keith D. Green, Abbygail C. Spencer, Oleg V. Tsodikov, Sylvie Garneau-Tsodikova
Summary: Novel substituted monohydrazides synthesized for this study demonstrated broad-spectrum activity against different fungal strains, including clinically relevant Candida auris strains. These compounds showed comparable or superior activity to amphotericin B against most of the tested fungal strains, along with fungistatic activity and no mammalian cell toxicity. They also inhibited the formation of fungal biofilms, and no resistance was developed by Candida albicans ATCC 10231 (strain A) even after repeated exposures.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Laura Prado-Alonso, Ignacio Perez-Victoria, Monica G. Malmierca, Ignacio Montero, Elisa Rioja-Blanco, Jesus Martin, Fernando Reyes, Carmen Mendez, Jose A. Salas, Carlos Olano
Summary: Genome mining has revealed the biosynthetic potential of actinomycetes and led to the discovery of novel halogenated bioactive compounds. In this study, a screening for halogenase coding genes in Streptomyces strains isolated from fungus-growing ants identified six genes. Mutants were constructed to study the biosynthetic gene clusters and a novel family of halogenated compounds, named colibrimycins, were identified in Streptomyces sp. strain CS147.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Farah Manzer Manhas, Shabnam Raheem, Jaswant Kumar, Pankaj Thakur, Masood Ahmad Rizvi
Summary: A novel transition metal-free photosensitized protocol has been developed for the synthesis of alpha-ketoamides via oxidative coupling of alkynes and amines in the presence of thiophenol under visible light irradiation and rose bengal dye. This reaction presents a benign visible light based milder synthetic methodology with broad functional-group tolerance.
Review
Pharmacology & Pharmacy
Alessio Nocentini, Clemente Capasso, Claudiu T. Supuran
Summary: Crystallography, previous drug design efforts, and many computational studies have provided a deeper understanding of the structural requirements for designing effective SARS-CoV-2 M-pro alpha-ketoamide inhibitors. However, all reported derivatives are peptidomimetics with a relatively high molecular weight. It is expected that future drug development will target effective compounds with lower molecular weights and a less peptidomimetic profile.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Chemistry, Medicinal
Xiaoxin Chen, Peng Li, Jianzhou Huang, Yaxun Yang, Haoyu Zhang, Zheng Wang, Zhenzhen Zhu, Jingjing Wang, Jianchen Zhang, Kevin Chen, Haiying He, Chaofeng Long, Shuhui Chen
Summary: The outbreak of SARS-CoV-2 has caused a global health and economic crisis. The use of Paxlovid requires specialized assessment of the multiple drug-drug interaction risk associated with ritonavir. We report a multiple-round SAR study that introduces a novel bicyclic [3.3.0]proline peptidyl a-ketoamide compound 4a, which exhibits excellent antiviral activities and pharmacokinetic properties. In vivo experiments using an HCoV-OC43 neonatal mice model demonstrate the good efficacy of compound 4a. Based on these findings, further SAR optimization is warranted to develop compounds with improved pharmacokinetic properties and ultimately achieve single agent efficacy in humans.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Applied
Han-Fu Liu, Yang Li, Guo-Ao Wang, Kai-Wei Chen, Hai-Tao Tang, Ying-Ming Pan, Mu-Xue He, Ke-Di Yang, Yong-Lin Huang
Summary: A feasible protocol has been developed for the synthesis of N-(a-alkoxyalkyl)benzotriazoles using azoles, aldehydes and alcohols as substrates under electrochemical conditions. The reaction can be carried out under acid catalyst- and oxidant-free conditions, allowing for the production of a variety of synthetically useful nitrogen heterocyclic derivatives. Moreover, a gram-scale synthetic approach was employed to demonstrate the scale-up applicability of this transformation.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Organic
Xiaoxiang Zhang, Wenhua Yu, Yiyu Nie, Yingying Zhang, Xiaoting Gu, Wanxing Wei, Zhuan Zhang, Taoyuan Liang
Summary: An efficient copper-iodine co-catalyzed method has been developed for the 2,3-difunctionalization of indoles with azoles and phenols, using a temperature-controlled selectivity switch. This strategy allows for the simultaneous establishment of C-C and C-N bonds in one operation, providing access to functionalized indoles with high regio-selectivity and good functional group compatibility. The utility of this method is demonstrated by the concise synthesis of an analogue of a potent anticancer agent. This work paves the way for further innovative direct difunctionalization of carbon-carbon double bonds.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Parasitology
Beatriz Munguia, Mauricio Michelena, Elisa Melian, Jenny Saldana, Ximena Ures, Eduardo Manta, Laura Dominguez
EXPERIMENTAL PARASITOLOGY
(2015)
Article
Parasitology
Beatriz Munguia, Ramiro Teixeira, Victoria Veroli, Elisa Melian, Jenny Saldana, Mahia Minteguiaga, Mario Senorale, Monica Marin, Laura Dominguez
EXPERIMENTAL PARASITOLOGY
(2017)
Article
Pharmacology & Pharmacy
M. Elisa Melian, A. Beatriz Munguia, Ricardo Faccio, Santiago Palma, Laura Dominguez
JOURNAL OF PHARMACEUTICAL INNOVATION
(2018)
Review
Biochemistry & Molecular Biology
M. Valli, A. Danuello, M. Pivatto, J. C. Saldana, H. Heinzen, L. Dominguez, V. P. Campos, S. R. Marqui, M. C. M. Young, C. Viegas, D. H. S. Silva, V. S. Bolzani
CURRENT MEDICINAL CHEMISTRY
(2011)
Article
Agricultural Engineering
A. Lopez, S. Castro, M. J. Andina, X. Ures, B. Munguia, J. M. Llabot, H. Elder, E. Dellacassa, S. Palma, L. Dominguez
INDUSTRIAL CROPS AND PRODUCTS
(2014)
Article
Parasitology
Andrea Medeiros, Maria Laura Chiribao, Luis Ubillos, Maria Florencia Festari, Jenny Saldana, Carlos Robello, Laura Dominguez, Juan Jose Calvete, Eduardo Osinaga
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2008)
Article
Biochemistry & Molecular Biology
Cecilia Socolsky, Laura Dominguez, Yoshinori Asakawa, Alicia Bardon
Article
Parasitology
Beatriz Munguia, Ramiro Teixeira, Maria Victoria Veroli, Monica Marin, Laura Dominguez
VETERINARY PARASITOLOGY- REGIONAL STUDIES AND REPORTS
(2018)
Article
Chemistry, Medicinal
G Mahler, G Serra, S Dematteis, J Saldaña, L Domínguez, E Manta
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2006)
Article
Parasitology
J Saldaña, M Marín, C Fernández, L Domínguez
PARASITOLOGY RESEARCH
(2001)
Article
Veterinary Sciences
L Domínguez, J Saldaña, J Chernin
CANADIAN JOURNAL OF VETERINARY RESEARCH-REVUE CANADIENNE DE RECHERCHE VETERINAIRE
(2000)
Article
Parasitology
Luis Ubillos, Andrea Medeiros, Martin Cancela, Cecilia Casaravilla, Jenny Saldana, Laura Dominguez, Carlos Carmona, Jacques Le Pendu, Eduardo Osinaga
EXPERIMENTAL PARASITOLOGY
(2007)
Article
Chemistry, Organic
Fuying Zhu, Yamei Lin
Summary: In this study, a low-metal iron-supported catalyst (Fe20/NC-Mg) was reported for the efficient synthesis of quinoxaline compounds, using water as a solvent and without additional bases. The synergistic effect of FeNx site and Mg (OH)2 nanorods in the catalyst played a key role in achieving high yields (82-91%) in 16 examples. The gram-level synthesis and reusability of the catalysts after four cycles demonstrated its industrial application potential.
Article
Chemistry, Organic
Mikhail Kozlov, Alexey Tyurin, Andrey Dmitrenok, Vyacheslav Rusak, Aleksander Fedorov, Igor Zavarzin, Yulia Volkova
Summary: This study presents a novel and practical synthesis method for phosphorus-substituted 1,3,4-thiadiazolines using phosphorylthioformic acid hydrazides and ketones. The protocol demonstrates operational simplicity, availability of reagents, and tolerance towards different functional groups.
Article
Chemistry, Organic
Jisna Jose, Thomas Mathew
Summary: 2-Cyclopentenone and its derivatives are highly esteemed synthetic intermediates with exceptional utility in organic synthesis. They are favored structural motifs in numerous pharmaceutical drugs and natural products, highlighting their significance. The review discusses the various methods used to synthesize cyclopentenones from 2016 to 2023.
