Article
Chemistry, Medicinal
Theresa Hermann, Patrick Hochegger, Johanna Dolensky, Werner Seebacher, Eva-Maria Pferschy-Wenzig, Robert Saf, Marcel Kaiser, Pascal Maeser, Robert Weis
Summary: The study synthesized and tested twenty-one derivatives, revealing structure-activity relationships and discussing the impact of substitution patterns and size on antiplasmodial activity and cytotoxicity. An optimized compound showed improved antiplasmodial activity, low cytotoxicity, and enhanced physicochemical and pharmacokinetic parameters compared to the lead structure.
Article
Biochemistry & Molecular Biology
Duc Hoang Lande, Abed Nasereddin, Arne Alder, Tim W. Gilberger, Ron Dzikowski, Johann Gruenefeld, Conrad Kunick
Summary: Malaria is a dangerous infectious disease for which novel antiplasmodial agents are needed due to parasite resistance. N-unsubstituted bisindolylcyclobutenediones were designed as potential drugs and showed promising antiplasmodial activity through molecular docking and synthesis.
Article
Biochemistry & Molecular Biology
Shicheng Hou, Shishao Liang, Chao Zhang, Yingmei Han, Jianhui Liang, Hongyu Hu, Xingeng Zhang, Chun Hu, Xiaoping Liu, Hong Zhang
Summary: The study designed a new structural framework for anti-cancer compounds using molecular hybridization strategy, and synthesized 16 new target compounds. Seven compounds were found to exhibit excellent antiproliferative activities against four different cancer cell lines, with minimal activities against normal cell lines. Compound 9b and 9d showed particularly outstanding activity against all four cancer cell lines, with IC50 values less than 3 micromolar for MCF7 and PC3 cell lines.
Article
Chemistry, Physical
Jae Hyeok Lee, Yu Bin Choi, Dong-Eun Kim, Hoon-Kyu Shin, Burm-Jong Lee
Summary: Polyacene-benzothiazole derivatives were synthesized and fabricated into OLED devices, with APBT device being the most stable and emitting the most intense color in the deep blue range according to CIE coordinates.
CHEMICAL PHYSICS LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Anna Jaromin, Anna Czopek, Silvia Parapini, Nicoletta Basilico, Ernest Misiak, Jerzy Gubernator, Agnieszka Zagorska
Summary: This study synthesized novel derivatives and conducted preliminary physicochemical characterization, showing strong inhibitory effects against Plasmodium falciparum, particularly the chloroquine-resistant strain. These molecules exhibited no hemolytic action on human erythrocytes and low toxicity on mammalian cell line.
Article
Chemistry, Applied
Ayelen Luczywo, Lucia G. Gonzalez, Anna C. C. Aguiar, Juliana Oliveira de Souza, Guilherme E. Souza, Glaucius Oliva, Luis F. Aguilar, Juan J. Casal, Rafael V. C. Guido, Silvia E. Asis, Marco Mellado
Summary: Inspired by natural products, indole alkaloids have been used as a nucleus to design new antimalarial drugs. Through structure-activity relationship analysis, it was found that the focused LUMO lobe on the specific molecular zone is related to inhibitory activity against P. falciparum.
NATURAL PRODUCT RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Timothy K. Beng, Mckenna Sax, Claire Borg
Summary: This study reveals that dithiodiglycolic anhydride can undergo formal cycloaddition with aryl aldimines to yield functionalized 4-thiazolidinones. 2-alkenyl-4-thiazolidinones can be obtained when 1,3-azadienes are used. These compounds serve as the core structure of various pharmaceuticals with diverse biological activities.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Leonardo S. A. Carneiro, Fernando Almeida-Souza, Yanne S. C. Lopes, Rachel C. Novas, Kaique B. A. Santos, Carolina B. P. Ligiero, Katia da S. Calabrese, Camilla D. Buarque
Summary: The new series of compounds showed promising activity against Leishmania parasites in vitro, with compound 17x identified as a potential candidate for anti-leishmaniasis drugs.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Wen-Yan Wang, Zi-Hui Yang, A-Liang Li, Qing-Song Liu, Yue Sun, Wen Gu
Summary: A series of novel 2-amino-4-aryl-pyrimidine derivatives of ursolic acid were designed, synthesized, and evaluated for their anticancer activities, with compound 7b showing potent cytotoxic activity against MCF-7 and HeLa cells. Further mechanism studies revealed that compound 7b could inhibit cell migration, induce cell cycle arrest, and trigger apoptosis through multiple pathways, including ROS generation and mitochondrial membrane potential regulation. Additionally, compound 7b was found to simultaneously suppress multiple signaling pathways, suggesting potential as a targeted anticancer agent.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Romain Mustiere, Prisca Lagardere, Sebastien Hutter, Viviana Dell'Orco, Nadia Amanzougaghene, Shahin Tajeri, Jean-Francois Franetich, Sophie Corvaisier, Marc Since, Aurelie Malzert-Freon, Nicolas Masurier, Vincent Lisowski, Pierre Verhaeghe, Dominique Mazier, Nadine Azas, Patrice Vanelle, Nicolas Primas
Summary: Gamhepathiopine (M1) is a multi-stage acting antiplasmodial compound with poor stability, insufficient solubility, and low permeability. In this study, we synthesized 20 new derivatives based on a scaffold hopping strategy from M1, and identified a promising candidate, furane bioisostere 3j, with improved solubility and intestinal permeability, as well as good antiplasmodial activity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Luis Escobar, Qingqing Sun, Pablo Ballester
Summary: Proteins exhibit high-binding affinity and selectivity, as well as remarkable catalytic performance. The synthesis of biomimetic receptors featuring sizable aromatic cavities equipped with converging polar groups has received considerable attention. Calix[4]pyrroles and their derivatives are considered valuable receptors owing to their ability to interact with a wide variety of electron-rich, neutral, and charged guests.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Review
Chemistry, Multidisciplinary
Luis Escobar, Qingqing Sun, Pablo Ballester
Summary: Proteins possess high-binding affinity and selectivity, as well as remarkable catalytic performance. Synthetic receptors with sizable aromatic cavities and converging polar groups have received considerable attention.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Yogesh Nandurkar, Abhijit Shinde, Manish R. Bhoye, Shivaji Jagadale, Pravin Chimaji Mhaske
Summary: A new series of 2-(5-aryl-1-phenyl-1H-pyrazol-3-yl)-4-aryl thiazoles (10a-ab) were synthesized and their structures were characterized. These derivatives showed good antibacterial and antifungal activity, making them potential lead compounds for the treatment of microbial infections.
Article
Biochemistry & Molecular Biology
Anna Jaromin, Beata Gryzlo, Marek Jamrozik, Silvia Parapini, Nicoletta Basilico, Marek Cegla, Donatella Taramelli, Agnieszka Zagorska
Summary: Malaria remains a major threat with drug resistance on the rise. New tetrahydro-beta-carbolines were synthesized and tested for antiplasmodial activity, with N-(3,3-dimethylbutyl)-1-octyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b] indole-3-carboxamide (7) showing the most promising results. Further research is being conducted on its potential mechanisms of action and delivery systems.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Eva Schaller, Andi Ma, Lisa Chiara Gosch, Adrian Klefenz, David Schaller, Nils Goehringer, Leonard Kaps, Detlef Schuppan, Andrea Volkamer, Rainer Schobert, Bernhard Biersack, Bianca Nitzsche, Michael Hoepfner
Summary: The new 2-(thien-2-yl)-acrylonitrile derivatives showed promising antineoplastic efficacy in hepatoma models, with two derivatives identified as inhibitors with preferential activity against VEGFR-2 tyrosine kinase through kinase profiling. Their mode of action included inducing apoptotic capsase-3 activity in hepatoma cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Pedro Salas-Ambrosio, Antoine Tronnet, Pierre Verhaeghe, Colin Bonduelle
Summary: Antimicrobial peptides are natural macromolecules made of amino acids and have the potential to be novel therapeutic agents. Polypeptide polymer analogues of AMPs show great potential as biomaterials with biomimetic and bioactive structures.
Article
Chemistry, Multidisciplinary
Pedro Salas-Ambrosio, Antoine Tronnet, Marc Since, Sandra Bourgeade-Delmas, Jean-Luc Stigliani, Amelie Vax, Sebastien Lecommandoux, Bruno Dupuy, Pierre Verhaeghe, Colin Bonduelle
Summary: This study presents a simple method for the synthesis of cyclic poly(alpha-peptoids) using LiHMDS promoted ring-expansion polymerization (REP) from N-alkylated-N-carboxyanhydrides (NNCA). The new method allows the use of lysine-like monomers in REP to design bioactive macrocycles with potential pharmaceutical applications against Clostridioides difficile. This novel approach offers a more efficient and straightforward route compared to traditional methods.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Medicinal
Dyhia Amrane, Christophe-Sebastien Arnold, Sebastien Hutter, Julen Sanz-Serrano, Miguel Collia, Amaya Azqueta, Lucie Paloque, Anita Cohen, Nadia Amanzougaghene, Shahin Tajeri, Jean-Francois Franetich, Dominique Mazier, Francoise Benoit-Vical, Pierre Verhaeghe, Nadine Azas, Patrice Vanelle, Cyrille Botte, Nicolas Primas
Summary: A new compound (3i) with potential anti-malarial activity was discovered, showing potent activity targeting the apicoplast in malaria parasites and exhibiting selectivity. The compound showed good performance in genotoxicity tests and primarily relied on the CCl3 group for antiplasmodial activity.
Article
Chemistry, Medicinal
Dyhia Amrane, Nicolas Primas, Christophe-Sebastien Arnold, Sebastien Hutter, Beatrice Louis, Julen Sanz-Serrano, Amaya Azqueta, Nadia Amanzougaghene, Shahin Tajeri, Dominique Mazier, Pierre Verhaeghe, Nadine Azas, Cyrille Botte, Patrice Vanelle
Summary: The discovery of a new drug target for antimalarials and the synthesis of compounds with antiplasmodial activity have been reported. One compound showed high selectivity and efficacy in in vitro experiments. Further biological investigations suggest that this compound may act by affecting the parasite's apicoplast.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Tiffany Rundstadler, Emmanuelle Mothes, Samir Amrane, Jean-Luc Stigliani, Pierre Verhaeghe, Genevieve Pratviel
Summary: G-quadruplex nucleic acids (G4s) are RNA and DNA secondary structures that regulate key biological processes and are potential targets for small molecule drugs. Gold(III) penta-cationic porphyrins, specific G4 ligands, can inhibit HIV-1 infectivity by interacting with G4s. A study on the structure/affinity relationship of gold(III) cationic porphyrins aims to identify the best candidate for functionalization and investigate the antiviral mechanism of action.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2021)
Article
Polymer Science
Pedro Salas-Ambrosio, Antoine Tronnet, Mostafa Badreldin, Luzangel Reyes, Marc Since, Sandra Bourgeade-Delmas, Bruno Dupuy, Pierre Verhaeghe, Colin Bonduelle
Summary: New macromolecular engineering approaches were developed to prepare star-like polypeptoids through ring-opening polymerization. Evaluation of their cytotoxicity on HepG2 human cell line and screening against a variety of Gram-positive and Gram-negative bacteria identified several compounds with both good and selective antimicrobial activity.
Article
Microbiology
Henriette Bosson-Vanga, Nicolas Primas, Jean-Francois Franetich, Catherine Lavazec, Lina Gomez, Kutub Ashraf, Maurel Tefit, Valerie Soulard, Nathalie Dereuddre-Bosquet, Roger Le Grand, Melanie Donnette, Romain Mustiere, Nadia Amanzougaghene, Shahin Tajeri, Peggy Suzanne, Aurelie Malzert-Freon, Sylvain Rault, Patrice Vanelle, Sebastien Hutter, Anita Cohen, Georges Snounou, Pierre Roques, Nadine Azas, Prisca Lagardere, Vincent Lisowski, Nicolas Masurier, Michel Nguyen, Lucie Paloque, Francoise Benoit-Vical, Pierre Verhaeghe, Dominique Mazier
Summary: This study presents a new chemical structure that is active against multiple stages of the human malaria parasite, including those resistant to artemisinins. The molecule also reduces transmission of the parasite to the mosquito vector in a mouse model. This new compound family shows promise for the development of novel antimalarial drugs with a unique multi-stage mechanism of action.
MICROBIOLOGY SPECTRUM
(2021)
Article
Chemistry, Medicinal
Prisca Lagardere, Romain Mustiere, Nadia Amanzougaghene, Sebastien Hutter, Jean-Francois Franetich, Nadine Azas, Patrice Vanelle, Pierre Verhaeghe, Nicolas Primas, Dominique Mazier, Nicolas Masurier, Vincent Lisowski
Summary: Malaria remains a major global health problem, and the development of drug resistance poses a challenge. A series of 4-substituted thieno[3,2-d]pyrimidines were found to exhibit activity against different stages of the malaria parasite, with the chloro analogue of Gamhepathiopine showing promising activity against both the erythrocytic and hepatic stages.
Article
Chemistry, Medicinal
Romain Paoli-Lombardo, Nicolas Primas, Sandra Bourgeade-Delmas, Sebastien Hutter, Alix Sournia-Saquet, Clotilde Boudot, Emilie Brenot, Caroline Castera-Ducros, Sophie Corvaisier, Marc Since, Aurelie Malzert-Freon, Bertrand Courtioux, Alexis Valentin, Pierre Verhaeghe, Nadine Azas, Pascal Rathelot, Patrice Vanelle
Summary: A new antileishmanial compound with good activity against the intracellular amastigote stage of L. infantum was discovered through synthesis of new derivatives and drug evaluation, showing low cytotoxicity and favorable physicochemical properties for further in vivo studies.
Article
Biochemistry & Molecular Biology
Nguyen-Hung Le, Patricia Constant, Samuel Tranier, Virginie Nahoum, Valerie Guillet, Laurent Maveyraud, Mamadou Daffe, Lionel Mourey, Pierre Verhaeghe, Hedia Marrakchi
Summary: Tuberculosis is a global health crisis with limited treatment options and drug resistance issues. Developing drugs targeting enzymes involved in cell envelope synthesis of Mycobacterium tuberculosis is crucial. Through a drug repurposing campaign, salicylanilide closantel and its derivatives were discovered as potential candidates for novel anti-tubercular drugs.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Romain Mustiere, Prisca Lagardere, Sebastien Hutter, Viviana Dell'Orco, Nadia Amanzougaghene, Shahin Tajeri, Jean-Francois Franetich, Sophie Corvaisier, Marc Since, Aurelie Malzert-Freon, Nicolas Masurier, Vincent Lisowski, Pierre Verhaeghe, Dominique Mazier, Nadine Azas, Patrice Vanelle, Nicolas Primas
Summary: Gamhepathiopine (M1) is a multi-stage acting antiplasmodial compound with poor stability, insufficient solubility, and low permeability. In this study, we synthesized 20 new derivatives based on a scaffold hopping strategy from M1, and identified a promising candidate, furane bioisostere 3j, with improved solubility and intestinal permeability, as well as good antiplasmodial activity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Prisca Lagardere, Romain Mustiere, Nadia Amanzougaghene, Sebastien Hutter, Marion Casanova, Jean-Francois Franetich, Shahin Tajeri, Aurelie Malzert-Freon, Sophie Corvaisier, Nadine Azas, Patrice Vanelle, Pierre Verhaeghe, Nicolas Primas, Dominique Mazier, Nicolas Masurier, Vincent Lisowski
Summary: The need for new compounds effective against multiple stages of Plasmodium falciparum development is urgent due to the increasing number of strains resistant to current treatments. In this study, 25 new 4-amino-substituted analogues based on Gamhepathiopine were synthesized and evaluated on both erythrocytic and hepatic stages of the parasite. A promising compound, N2-(tert-butyl)-N [4]-(3-(dimethylamino)propyl)-6-(p-tolyl)thieno[3,2-d]pyrimidine-2,4-diamine, showed improved physicochemical properties, intestinal permeability, and microsomal stability compared to Gamhepathiopine, while maintaining good anti-plasmodial activity on the erythrocytic and hepatic stages of Plasmodium falciparum and P. berghei.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Prisca Lagardere, Romain Mustiere, Nadia Amanzougaghene, Sebastien Hutter, Marion Casanova, Jean-Francois Franetich, Shahin Tajeri, Aurelie Malzert-Freon, Sophie Corvaisier, Marc Since, Nadine Azas, Patrice Vanelle, Pierre Verhaeghe, Nicolas Primas, Dominique Mazier, Nicolas Masurier, Vincent Lisowski
Summary: In this study, several strategies were explored to improve the metabolic stability of a previously identified compound with promising antiplasmodial activity. Among the new compounds, the 2-aminocyclobutyl derivative 5g exhibited enhanced microsomal stability and maintained antiplasmodial activity against erythrocytic and hepatic stages of Plasmodium, without significant cytotoxicity against primary hepatocytes.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Polymer Science
Pedro Salas-Ambrosio, Antoine Tronnet, Mostafa Badreldin, Sifan Ji, Sebastien Lecommandoux, Simon Harrisson, Pierre Verhaeghe, Colin Bonduelle
Summary: This report provides a comprehensive study on the contribution of the N-alkyl group to the synthesis of NNCA and its reactivity in polymerization reactions. We found that electron-donating groups can enhance the kinetic rates of polymerization reactions.
Article
Chemistry, Multidisciplinary
Romain Mustiere, Prisca Lagardere, Sebastien Hutter, Celine Deraeve, Florian Schwalen, Dyhia Amrane, Nicolas Masurier, Nadine Azas, Vincent Lisowski, Pierre Verhaeghe, Dominique Mazier, Patrice Vanelle, Nicolas Primas
Summary: This study describes the synthesis of 33 new compounds in the 2-aminothieno[3,2-d]pyrimidin-4(3H)-one series via three palladium-catalyzed cross coupling reactions. The synthesized compounds were evaluated for their antiplasmodial activity and cytotoxicity. Although a better compound than the existing drug was not obtained, compound 1g with improved cytotoxicity and metabolic stability was identified as a potential starting point for further research.
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
