Article
Chemistry, Organic
Yuting Gao, Yang Sun, Xianfu Fang, Guixian Zhao, Xufeng Li, Gong Zhang, Yangfeng Li, Yizhou Li
Summary: The DNA-encoded chemical library (DEL) technology, with the incorporation of vinyl sulfone, enables mild and efficient DNA-compatible synthesis, demonstrating the feasibility of DEL construction.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Biochemistry & Molecular Biology
Viharika Bobba, Yaxin Li, Marjia Afrin, Raina Dano, Wenjing Zhang, Bibo Li, Bin Su
Summary: Researchers have developed a selective drug candidate library for the treatment of Human African trypanosomiasis. One compound in particular has shown high potency and selectively inhibits the growth of trypanosome cells. Further studies will guide future optimization efforts.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yongzhi Chen, Hongxia Li, Jiayong Liu, Rongcui Zhong, Haizhou Li, Shanfang Fang, Shouping Liu, Shuimu Lin
Summary: The emergence of bacterial multidrug resistance and the lack of new antimicrobial agents have led to the urgent need for the discovery and development of novel antibacterials. Antimicrobial peptidomimetics have shown promise in overcoming antibiotic resistance and are effective in rapidly killing bacteria without inducing resistance. Specific compounds have demonstrated potent activity against Gram-positive bacteria, low toxicity to mammalian cells, good stability, and high efficacy in treating bacterial infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Van Hai Nguyen, Michal Tichy, Samanta Rozankova, Radek Pohl, A. Michael Downey, Eva Dolezelova, Eva Tloustova, Martina Slapnickova, Alena Zikova, Michal Hocek
Summary: A novel class of 3'-deoxy-3'-fluororibonucleosides derived from 7-deazaadenine nucleosides showed promising antitrypanosomal activity against Trypanosoma brucei brucei, with the 7-bromo- and 7-iododerivatives being the most active and non-cytotoxic. These compounds could be potential candidates for further development as new treatments for Human African Trypanosomiasis.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Dan Wan, Feng-Qin Wang, Jiang Xie, Lin Chen, Xian-Li Zhou
Summary: In this study, multifunctional hybrid compounds were obtained by connecting benzylpiperidine with phenylethylamine. Compound 3 exhibited excellent acetylcholinesterase inhibitory activity and neuroprotective effects. Molecular docking research indicated that the square amide group formed strong interactions with the target protein. Therefore, square amide could be an interesting construction unit in anti-Alzheimer’s disease agents.
Article
Biochemistry & Molecular Biology
Jignasa Savjani, Bhavesh Variya, Snehal Patel, Suja Mulamkattil, Harsh Amin, Shital Butani, Ahmed Allam, Jamaan Ajarem, Harsh Shah
Summary: This study developed a novel series of indomethacin analogues with potential anti-inflammatory properties and fewer side effects. Through various scientific approaches, the binding interactions between these analogues and COX-2 protein were evaluated, and the top-scoring complex was selected. In vitro and in vivo evaluations demonstrated that certain compounds exhibited strong COX-2 inhibition and anti-inflammatory potential without ulcerogenic liability.
Article
Chemistry, Organic
Lizeth Bodero, Sara Parente, Federico Arrigoni, Annika Klimpel, Ines Neundorf, Silvia Gazzola, Umberto Piarulli
Summary: Two new Drug Delivery Systems (DDS) containing the cyclo[DKP-isoDGR] integrin ligand and the cytotoxic agent Paclitaxel (PTX) were synthesized to investigate their influences on cellular uptake and cytotoxicity. Compound 3 showed significantly higher potency compared to compound 2, with reduced potency loss in comparison to PTX.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Reza Ahmadi, Saeed Emami
Summary: Vinyl sulfone is an important organic compound with a unique chemical structure, playing a significant role in drug discovery and development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Carina Lemke, Adela Jilkova, Dominic Ferber, Annett Braune, Anja On, Patrick Johe, Alena Zikova, Tanja Schirmeister, Michael Mares, Martin Horn, Michael Gutschow
Summary: We developed a bimodal rhodesain probe that can detect and quantify rhodesain with high sensitivity, and used it for inhibitor screening. This probe provides a new tool for studying Trypanosoma pathobiochemistry and antitrypanosomal drug discovery.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Medicinal
Hanxi Yang, Mengyuan You, Xiaoyang Shu, Jingyao Zhen, Mengwei Zhu, Tiantian Fu, Yan Zhang, Xiangrui Jiang, Leike Zhang, Yechun Xu, Yumin Zhang, Haixia Su, Qiumeng Zhang, Jingshan Shen
Summary: A series of peptidomimetic compounds containing benzothiazolyl ketone and [2.2.1] azabicyclic ring were synthesized and evaluated for their inhibition of SARS-CoV-2 3CLpro. Compound 11j showed the best enzyme inhibition activity and exhibited significant anti-SARS-CoV-2 activity with low cytotoxicity. It displayed promising pharmacokinetic properties and could serve as a lead compound for further development of oral 3CLpro inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biology
Jorge Gonzalez-Bacerio, Irina Arocha, Mirtha Elisa Aguado, Yanira Mendez, Sabrina Marsiccobetre, Maikel Izquierdo, Daniel G. Rivera, Katherine Figarella, Nestor L. Uzcategui
Summary: The research discovered that the peptidomimetic KBE009 inhibits TcLAP and proliferative activity of T. cruzi in vitro with selectivity for the parasite over human cells. Docking simulations using crystal structures showed KBE009 had better geometrical shape and stability in TcLAP compared to its human orthologous hLAP3, suggesting potential as a starting compound for drug design.
Article
Chemistry, Organic
Seunghwan An, Kwang Ho Song, Sunwoo Lee
Summary: The synthesis of vinyl sulfone derivatives via the reaction of arylpropiolic acids, K2S2O5, and aryl boronic acids using the CuBr2/1,10-phenanthroline catalytic system in the presence of acetic acid provides the desired products in moderate to good yield, showcasing excellent functional group tolerance.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Shanfang Fang, Yuan-Ye Dang, Haizhou Li, Hongxia Li, Jiayong Liu, Rongcui Zhong, Yongzhi Chen, Shouping Liu, Shuimu Lin
Summary: Bacteria have become more resistant to current antimicrobial drugs. New antimicrobial drugs are urgently needed to combat drug-resistant pathogens. In this study, we designed and synthesized a series of calix[4]arene derivatives as antibacterial agents, mimicking the structure and functions of antibacterial peptides. After introducing cationic hydrophilic moieties and optimizing the structure, we identified a lead compound (16) with excellent antibacterial activity against Gram-positive bacteria, low toxicity to mammalian cells, and poor hemolytic activity. The mechanism studies showed that compound 16 can directly destroy bacterial cell membranes, leading to bacterial death and low potential for bacterial resistance development.
FRONTIERS IN CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ivo E. Sampaio-Dias, Miguel Santejo, Sara C. Silva-Reis, Marcia A. Liz, Cristina Alcoholado, Manuel Algarra, Xerardo Garcia-Mera, Jose E. Rodriguez-Borges
Summary: Neurodegenerative disorders of the central nervous system represent a global health burden, and research on neuroprotective drugs is considered a health priority. The new analogues designed and synthesized in this study show potential in neuroprotection assays.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Chemistry, Physical
Banoth Venkateswara Rao, Sonam Swain, Bandi Siva, S. V. S. Sasi Priya, Surender Singh Jadav, Nishant Jain, Vaikundamoorthy Ramalingam, K. Suresh Babu
Summary: Novel bergenin hybrids containing sulfonate and 1, 2, 3-triazole moieties at carbon-11 were designed and synthesized as potential anti-mitotic tubulin inhibitors. In vitro cytotoxic activity evaluation against various cancer cells showed that the majority of these derivatives exhibited potent anticancer activity, with compounds 3i, 6g, and 6h demonstrating significant activity against HeLa cell line. Flow cytometry analysis confirmed G2/M phase arrest, increased expression of mitotic markers, and induction of apoptosis by these compounds. Molecular docking studies revealed their significant binding energy with PLK1 and Cyclin B1 proteins.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Biochemistry & Molecular Biology
Miriam Carr, Andrew J. S. Knox, Daniel K. Nevin, Niamh O'Boyle, Shu Wang, Billy Egan, Thomas McCabe, Brendan Twamley, Daniela M. Zisterer, David G. Lloyd, Mary J. Meegan
BIOORGANIC & MEDICINAL CHEMISTRY
(2020)
Review
Biochemistry & Molecular Biology
Heta Jigar Panchal, Nigel J. Kent, Andrew J. S. Knox, Leanne F. Harris
Article
Biochemistry & Molecular Biology
William Doherty, Nikoletta Adler, Thomas J. Butler, Andrew J. S. Knox, Paul Evans
BIOORGANIC & MEDICINAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Mark Berney, William Doherty, Werner Theodor Jauslin, Manav T. Manoj, Eva-Maria Durr, Joanna Francelle McGouran
Summary: This study focused on synthesizing nucleoside derivatives with squaramide and thiosquaramide for evaluation as SNM1A inhibitors. The thymidine derivative with a 5'-thiosquaramide was found to be the most potent inhibitor, followed by a thymidine derivative with a 3'-squaric acid. UV-Vis titrations were used to assess the binding of (thio)squaramides to zinc ions, providing insight into their inhibitory potency. Membrane permeability of the active inhibitors was also investigated, with some compounds showing promise for future in vivo applications.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Review
Immunology
Etienne Pays, Derek P. Nolan
Summary: Human African trypanosomiasis, or sleeping sickness, is caused by two subspecies of the protozoan parasite Trypanosoma brucei, which can evade human serum killing, evolve strategies to counteract host immune defenses, and the main parasite surface antigen VSG plays a critical role in interactions with the host.
CURRENT OPINION IN IMMUNOLOGY
(2021)
Article
Immunology
Ciana Diskin, Sarah E. Corcoran, Victoria J. Tyrrell, Anne F. McGettrick, Zbigniew Zaslona, Valerie B. O'Donnell, Derek P. Nolan, Luke A. J. O'Neill
Summary: Trypanosoma brucei, the causative agent of human African trypanosomiasis, secretes a metabolite that inhibits specific protein production in macrophages, potentially promoting the survival of both the host and the parasite.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Lorna Conway, Paul Evans
Summary: Routes are reported for the synthesis of both (1R)- and (1S)-tert-butyl-(4-oxocyclopent-2-en-1-yl)carbamate 2 utilizing Mitsunobu reactions. These syntheses start from the optically active starting material (S)-4-[(tert-butyldimethylsilyl)oxy]cyclopent-2-en-1-one (3) and achieve enantiodivergent access to (-)- and (+)-2 in 11% and 10% overall yield, respectively, over five and seven reaction steps.
JOURNAL OF CHEMICAL RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Rory Whelan, Grainne C. Hargaden, Andrew J. S. Knox
Summary: This review summarizes various classes of BBB modulators developed over the last five decades, discussing their recent advancements, advantages and disadvantages, while providing insight into their future as BBB modulators.
Article
Biochemistry & Molecular Biology
Hannah K. Fitzgerald, Sinead A. O'Rourke, Eva Desmond, Nuno G. B. Neto, Michael G. Monaghan, Miriam Tosetto, Jayne Doherty, Elizabeth J. Ryan, Glen A. Doherty, Derek P. Nolan, Jean M. Fletcher, Aisling Dunne
Summary: This study found that the derived ketoacids from the extracellular parasite Trypanosoma brucei can induce HO-1 expression and suppress inflammatory responses in human dendritic cells. They also have the ability to modulate cellular metabolism and suppress the inflammatory profile of cells from patients with inflammatory bowel disease.
Article
Biochemistry & Molecular Biology
Daniela D. Queiroz, Thales de P. Ribeiro, Julliana M. Goncalves, Larissa M. M. Mattos, Ellen Gerhardt, Julia Freitas, Fernando L. Palhano, Susana Frases, Anderson S. Pinheiro, Malachy McCann, Andrew Knox, Michael Devereux, Tiago F. Outeiro, Marcos D. Pereira
Summary: The overproduction of reactive oxygen species (ROS) induces oxidative stress, which is associated with aging and various human pathologies. This study investigates the antioxidant activity of a water-soluble Mn2+-complex and its ability to attenuate alpha-synuclein toxicity and aggregation. The Mn2+-complex exhibits significant antioxidant potential and increases the activity of intracellular antioxidant enzymes, while also reducing alpha-synuclein oligomerization and aggregation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Chemistry, Organic
Aisha Khalifa, Robert Redmond, Goar Sanchez-Sanz, Paul Evans
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Dandan Lin, Anna Sullivan, Martha Circeie, Vittoria Chiericoni, Jaroslav Karpov, Kacper Kluza, Niamh O'Neill, Wilhelm Risse, Paul Evans
Summary: This study investigates the ring-closing enyne metathesis of a series of enynes containing sulfone groups. The reaction produces 1,1-dioxides (sulfolenes) and 1,1-dioxothiophenes through cyclization. The success of the reaction depends on the substitution pattern of the substrate and the reaction conditions used.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Raed K. Zaidan, Paul Evans
Summary: The preparation of six new optically active analogues of the natural product febrifugine is reported. These analogues were prepared by a series of chemical reactions and lack the hydroxy group found in the natural product.
JOURNAL OF CHEMICAL RESEARCH
(2022)
Meeting Abstract
Immunology
Hannah K. Fitzgerald, David G. Williams, Nicole K. Campbell, Paul J. Barry, Sinead A. O'Rourke, Nuno G. Neto, Michael G. Monaghan, Derek P. Nolan, Aisling Dunne
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
