Article
Multidisciplinary Sciences
Michael Gerckens, Kenji Schorpp, Francesco Pelizza, Melanie Woegrath, Kora Reichau, Huilong Ma, Armando-Marco Dworsky, Arunima Sengupta, Mircea Gabriel Stoleriu, Katharina Heinzelmann, Juliane Merl-Pham, Martin Irmler, Hani N. Alsafadi, Eduard Trenkenschuh, Lenka Sarnova, Marketa Jirouskova, Wolfgang Friess, Stefanie M. Hauck, Johannes Beckers, Nikolaus Kneidinger, Juergen Behr, Anne Hilgendorff, Kamyar Hadian, Michael Lindner, Melanie Koenigshoff, Oliver Eickelberg, Martin Gregor, Oliver Plettenburg, Ali Oender Yildirim, Gerald Burgstaller
Summary: A novel class of compounds, N23Ps, was discovered to inhibit organ fibrosis by suppressing myofibroblast transdifferentiation and ECM deposition. The mechanism of action includes targeting a potential therapeutic network identified through transcriptomics. These compounds were shown to effectively reduce organ damage caused by chronic diseases.
Article
Biochemistry & Molecular Biology
Daniel Cordova, Eric A. Benner, David A. Clark, Stephen P. Bolgunas, George P. Lahm, Steven Gutteridge, Daniel F. Rhoades, Lihong Wu, Jeffrey S. Sopa, James J. Rauh, James D. Barry
Summary: The Ryanodine receptor (RyR) is an intracellular calcium channel critical for regulating insect muscle contraction and is the target site of diamide insecticides. A new class of RyR activators, pyrrole-2carboxamides, has been discovered through target-based screening, showing comparable potency to commercial diamides against fruit fly RyR. However, poor insecticidal activity in whole-insect screens is attributed to differential selectivity among insect receptors and rapid detoxification.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Mihaela Peric, Dijana Pesic, Sulejman Alihodzic, Andrea Fajdetic, Esperanza Herreros, Francisco Javier Gamo, Inigo Angulo-Barturen, Maria Belen Jimenez-Diaz, Santiago Ferrer-Bazaga, Maria S. Martinez, Domingo Gargallo-Viola, Amanda Mathis, Albane Kessler, Mihailo Banjanac, Jasna Padovan, Vlatka Bencetic Mihaljevic, Vesna Munic Kos, Mirjana Bukvic, Vesna Erakovic Haber, Radan Spaventi
Summary: Novel fast-acting azalides showed high activity against drug-resistant Plasmodium falciparum in vitro and demonstrated excellent antimalarial activity in a murine model. Pharmacokinetic analysis revealed stable metabolism, making these compounds ideal candidates for antimalarial therapy.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Anuradha Kumar, Somsundaram Chettiar, Brian S. Brown, Julie Early, Juliane Ollinger, Megan Files, Mai A. Bailey, Aaron Korkegian, Devon Dennison, Matthew McNeil, James Metz, Augustine Osuma, Michael Curtin, Aaron Kunzer, Gail Freiberg, Milan Bruncko, Dale Kempf, Tanya Parish
Summary: A high-throughput phenotypic screening of a diverse chemical library identified 24 chemotypes with anti-tubercular activity. Further exploration revealed that MmpL3 may serve as the target or mechanism of resistance for these compounds.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Medicinal
Reem A. Wagdy, Nader S. Abutaleb, Reem K. Fathalla, Yehia Elgammal, Stefanie Weck, Rusha Pal, Patrick D. Fischer, Christian Ducho, Ashraf H. Abadi, Mohamed N. Seleem, Matthias Engel, Mohammad Abdel-Halim
Summary: The synthesis of novel compounds targeting the cytoplasmic steps of peptidoglycan synthesis as potential antibacterial agents was reported. Some of these compounds showed potent inhibition of MurA enzyme and exhibited antibacterial activity against Clostridioides difficile strains. The inhibition of MurA enzyme was found to be responsible for the observed effect on bacterial growth.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Kseniya Glinkina, Arwin Groenewoud, Amina F. A. S. Teunisse, B. Ewa Snaar-Jagalska, Aart G. Jochemsen
Summary: In this study, we used CRISPR-Cas9 synthetic lethality screening to identify molecular targets that can enhance the effect of everolimus in uveal melanoma cells. IGF1R and PRKDC were among the hits, and their synergy with everolimus was confirmed. The dual DNA-PKcs/mTOR inhibitor CC-115 showed significant activity in an in vivo model.
Article
Chemistry, Analytical
Oleksandr Matvieiev, Renata Selesovska, Marian Vojs, Marian Marton, Pavol Michniak, Vojtech Hrdlicka, Michal Hatala, Lenka Janikova, Jaromira Chylkova, Jana Skopalova, Petr Cankar, Tomas Navratil
Summary: A new screen-printed sensor with a boron-doped diamond working electrode was fabricated using a large-area linear antenna microwave chemical deposition vapor system. The sensor combines the advantages of disposable printed sensors with the excellent electrochemical properties of the boron-doped diamond electrode. The sensor's feasibility and applicability were verified through various experiments and analysis.
Article
Microbiology
Migla Miskinyte, John C. Dawson, Ashraff Makda, Dahlia Doughty-Shenton, Neil O. Carragher, Achim Schnaufer
Summary: In this study, we developed a high-content screen for pharmacologically induced kDNA loss in kinetoplastid parasites and identified a novel kDNA-targeting compound as a validated hit.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Genetics & Heredity
Qing Xin, Yameng Dong, Wencong Guo, Xiangzhong Zhao, Zhiying Liu, Xiaomeng Shi, Yanhua Lang, Leping Shao
Summary: This study analyzed the genotype of 21 Chinese patients with primary hyperoxaluria (PH) and identified correlations between genotype and phenotype. Four novel variants were found and the study expanded the variant spectrum of PH in the Chinese population.
FRONTIERS IN GENETICS
(2023)
Article
Spectroscopy
Kaliyan Prabakaran, Hyeon Oh, Ramalingam Manivannan, Si Hyeong Park, Young-A Son
Summary: In this paper, a new class of chemically linked UV absorber XU2 & XU3 was prepared and their photophysical, chemical properties and substrate durability were investigated. The synthesized XU2 & XU3 showed good absorbance and emission band maxima at all solvents and pH mediums, making them potential UV protectants.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2022)
Article
Chemistry, Multidisciplinary
Usama B. Farrukh, Aishah Bilal, Huda Zahid, Maheen Iqbal, Safia Manzoor, Farhat Firdous, Muhammad Furqan, Muhammad Azeem, Abdul-Hamid Emwas, Meshari Alazmi, Xin Gao, Rahman S. Z. Saleem, Amir Faisal
Summary: In this study, a novel compound 5h was identified as an inhibitor of centrosome clustering in breast cancer cells. Treatment with 5h resulted in mitotic arrest and apoptotic cell death.
Article
Chemistry, Medicinal
Jopaul Mathew, Sha Ding, Kevin A. Kunz, Emily E. Stacy, Joshua H. Butler, Reagan S. Haney, Emilio F. Merino, Grant J. Butschek, Zaira Rizopoulos, Maxim Totrov, Maria B. Cassera, Paul R. Carlier
Summary: Virtual ligand screening using a pharmacophore derived from antimalarial MMV008138 led to the identification of TCMDC-140230 as a compound worth exploring. However, none of the four stereoisomers synthesized showed potent inhibition of Plasmodium falciparum growth, while a minor byproduct 7e exhibited strong in vitro antimalarial activity and was orally efficacious in an in vivo mouse model of malaria.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Editorial Material
Cell Biology
Alison Gareau, Ahmad Abu-Khader, Guang Yang, Luz Stamm, Noureddine Berka
Summary: This article describes four novel HLA class II alleles identified in our laboratory through the implementation of next generation sequencing, improving our ability to match at all clinically relevant HLA loci and facilitating the interpretation of allele specific antibody and eplet matching.
Article
Chemistry, Medicinal
Fei-Fei Yang, Jin-Zhu Zhou, Xue-Li Xu, Ting Hu, Jian-Quan Liu, Ya-Xi Wu, Bo Wei, Li-Ying Ma
Summary: This study discovered a compound containing 1,3,4-oxadiazole that showed potential protective activity against oxidative stress in cardiomyocytes. The study also highlighted the importance of substitution sites and bisamide moiety in enhancing the protective activity. This finding provides new choices for the optimization of cardiovascular drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Organic
Sarah Zinken, Axel Pahl, Michael Grigalunas, Herbert Waldmann
Summary: Chromaline pseudo-natural products are a collection of topologically diverse compounds that were designed to access novel biological space by combining chromane and 4H-quinoline natural product fragments. The compounds possess both drug-like and natural product-like properties and have distinct bioactivity profiles compared to previous pseudo-natural product collections. This suggests that the new fragment combination may have led to a unique bioactivity.
Article
Pharmacology & Pharmacy
Mihaela Peric, Dijana Pesic, Sulejman Alihodzic, Andrea Fajdetic, Esperanza Herreros, Francisco Javier Gamo, Inigo Angulo-Barturen, Maria Belen Jimenez-Diaz, Santiago Ferrer-Bazaga, Maria S. Martinez, Domingo Gargallo-Viola, Amanda Mathis, Albane Kessler, Mihailo Banjanac, Jasna Padovan, Vlatka Bencetic Mihaljevic, Vesna Munic Kos, Mirjana Bukvic, Vesna Erakovic Haber, Radan Spaventi
Summary: Novel fast-acting azalides showed high activity against drug-resistant Plasmodium falciparum in vitro and demonstrated excellent antimalarial activity in a murine model. Pharmacokinetic analysis revealed stable metabolism, making these compounds ideal candidates for antimalarial therapy.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Sarah Preston, Jose Garcia-Bustos, Liam G. Hall, Sheree D. Martin, Thuy G. Le, Abhijit Kundu, Atanu Ghoshal, Nghi H. Nguyen, Yaqing Jiao, Banfeng Ruan, Lian Xue, Fei Huang, Bill C. H. Chang, Sean L. McGee, Timothy N. C. Wells, Michael J. Palmer, Abdul Jabbar, Robin B. Gasser, Jonathan B. Baell
Summary: A series of novel compounds were synthesized as potent inhibitors of Haemonchus contortus, the parasitic nematode of sheep, showing high selectivity in mammalian cell lines but causing acute toxicity in rodents, possibly due to respiratory inhibition. Additionally, potent cytotoxicity was observed in rat hepatocytes, unrelated to toxicity in respiring cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Infectious Diseases
Andrew A. Voak, Andy Harris, Jose Miguel Coteron-Lopez, Inigo Angulo-Barturen, Santiago Ferrer-Bazaga, Simon L. Croft, Karin Seifert
Summary: This study characterized the pharmacokinetic and pharmacodynamic properties of anti-leishmanial drugs AmBisome and miltefosine in a mouse model of visceral leishmaniasis. Optimal dosing strategies for AmBisome were proposed, demonstrating a wider therapeutic range compared to miltefosine. The study also highlighted the importance of using animal models in drug development for visceral leishmaniasis.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Chemistry, Medicinal
Michael J. Palmer, Xiaoyi Deng, Shawn Watts, Goran Krilov, Aleksey Gerasyuto, Sreekanth Kokkonda, Farah El Mazouni, John White, Karen L. White, Josefine Striepen, Jade Bath, Kyra A. Schindler, Tomas Yeo, David M. Shackleford, Sachel Mok, Ioanna Deni, Aloysus Lawong, Ann Huang, Gong Chen, Wen Wang, Jaya Jayaseelan, Kasiram Katneni, Rahul Patil, Jessica Saunders, Shatrughan P. Shahi, Rajesh Chittimalla, Inigo Angulo-Barturen, Maria Belen Jimenez-Diaz, Sergio Wittlin, Patrick K. Tumwebaze, Philip J. Rosenthal, Roland A. Cooper, Anna Caroline Campos Aguiar, Rafael V. C. Guido, Dhelio B. Pereira, Nimisha Mittal, Elizabeth A. Winzeler, Diana R. Tomchick, Benoit Laleu, Jeremy N. Burrows, Pradipsinh K. Rathod, David A. Fidock, Susan A. Charman, Margaret A. Phillips
Summary: DHODH has been clinically validated as a target for new antimalarials, and a structure-based computationally driven lead optimization program of DHODH inhibitors has led to the discovery of two promising candidates for potential advancement to preclinical development. These compounds exhibit improved physicochemical properties, potent antimalarial activity in vitro, and good efficacy in Plasmodium falciparum SCID mouse models, showing selectivity for Plasmodium DHODHs versus mammalian enzymes.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Zita Sulyok, Rolf Fendel, Bianca Eder, Freia-Raphaella Lorenz, K. C. Natasha, Matthias Karnahl, Albert Lalremruata, The T. Nguyen, Jana Held, Folashade Almeine Cyntiche Adjadi, Torsten Klockenbring, Judith Flugge, Tamirat Gebru Woldearegai, Carlos Lamsfus Calle, Javier Ibanez, Miriam Rodi, Diane Egger-Adam, Andrea Kreidenweiss, Carsten Kohler, Meral Esen, Mihaly Sulyok, Anita Manoj, Thomas L. Richie, B. Kim Lee Sim, Stephen L. Hoffman, Benjamin Mordmuller, Peter G. Kremsner
Summary: The study reports the results of a trial on a simplified PfSPZ-CVac immunization regimen, demonstrating its high efficacy, safety, good tolerability, and high immunogenicity in malaria-naive participants.
NATURE COMMUNICATIONS
(2021)
Article
Infectious Diseases
Odilon Nouatin, Juliana Boex Mengue, Jean Claude Dejon-Agobe, Rolf Fendel, Javier Ibanez, Ulysse Ateba Ngoa, Jean Ronald Edoa, Bayode Romeo Adegbite, Yabo Josiane Honkpehedji, Jeannot Frejus Zinsou, Aurore Bouyoukou Hounkpatin, Kabirou Moutairou, Andreas Homoet, Meral Esen, Andrea Kreidenweiss, Stephen L. Hoffman, Michael Theisen, Adrian J. F. Luty, Bertrand Lell, Selidji Todagbe Agnandji, Ghyslain Mombo-Ngoma, Michael Ramharter, Peter Kremsner, Benjamin Mordmueller, Ayola Akim Adegnika
Summary: Helminth infections, particularly Schistosoma haematobium and soil-transmitted helminths, were found to be significantly associated with earlier malaria episodes following controlled human malaria infection. In the absence of helminth infection, a high anti-GMZ2 IgG concentration was significantly associated with protection against malaria. These results suggest that helminth infection may affect malaria vaccine immunogenicity and efficacy in endemic countries.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Chemistry, Medicinal
Lydia Mata-Cantero, Stanley C. Xie, Mercedes Garcia, Joanne Coyle, Raquel Fernandez, Alvaro Cortes Cabrera, David L. Gillett, Benigno Crespo, Francisco-Javier Gamo, Esther Fernandez, Leann Tilley, Maria G. Gomez-Lorenzo
Summary: Through screening compounds, this study identified four chemical families with selectivity for the P. falciparum proteasome, providing a good starting point for the development of new antimalarial drugs.
ACS INFECTIOUS DISEASES
(2021)
Article
Infectious Diseases
Wilson Lim, Bertrand Nyuykonge, Kimberly Eadie, Mickey Konings, Juli Smeets, Ahmed Fahal, Alexandro Bonifaz, Matthew Todd, Benjamin Perry, Kirandeep Samby, Jeremy Burrows, Annelies Verbon, Wendy van de Sande
Summary: Eumycetoma is a chronic subcutaneous neglected tropical disease caused by various fungal agents. Current antifungal drugs have low cure rates, and there is a need for novel treatments. In this study, four compounds (fenbendazole, carbendazim, tafenoquine, and MMV1578570) were found to inhibit the growth of five species of fungi that cause eumycetoma. These compounds showed promising results in in vivo experiments as well.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Pharmacology & Pharmacy
Morris Muliaditan, Donato Teutonico, Fatima Ortega-Muro, Santiago Ferrer, Oscar Della Pasqua
Summary: This study used whole-body physiologically-based pharmacokinetic (PBPK) modeling based on plasma data in mice to predict lung exposure to anti-tubercular drugs in humans. The predicted lung exposures were comparable to plasma levels for isoniazid and pyrazinamide, but higher than plasma for ethambutol. This suggests that combining plasma pharmacokinetics with PBPK modeling can be used to derive lung tissue exposure in mice and humans during the early optimization phase of tuberculosis drug development.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Editorial Material
Infectious Diseases
Claudia Daubenberger, Jeremy N. Burrows
LANCET INFECTIOUS DISEASES
(2022)
Article
Immunology
Javier Ibanez, Rolf Fendel, Freia-Raphaella Lorenz, Patricia Granados-Bayon, Sina Brueckner, Meral Esen, Mihaly Sulyok, Zita Sulyok, Steffen Borrmann, Petra Bacher, Alexander Scheffold, Stephen L. Hoffman, Peter G. Kremsner, Benjamin Mordmueller
Summary: This study tested two accelerated three-dose schedules for malaria vaccination and found that the 10-day regimen had better outcomes in inducing specific T cell and antibody responses. The shorter vaccination interval may lead to a longer exposure to liver-stage parasites, which contributes to a stronger immune response.
Article
Infectious Diseases
Odilon Nouatin, Javier Ibanez, Rolf Fendel, Ulysse A. Ngoa, Freia-Raphaella Lorenz, Jean-Claude Dejon-Agobe, Jean Ronald Edoa, Judith Fluegge, Sina Brueckner, Meral Esen, Michael Theisen, Stephen L. Hoffman, Kabirou Moutairou, Adrian J. F. Luty, Bertrand Lell, Peter G. Kremsner, Ayola A. Adegnika, Benjamin Mordmueller
Summary: In a vaccine trial investigating the malaria vaccine candidate GMZ2, it was found that the GMZ2-specific antibody response increased after vaccination but was not correlated to protection. However, antibody responses to several Plasmodium falciparum antigens and the broadness of malaria-specific antibody response were significantly higher in protected study participants.
Article
Virology
Lucca R. Policastro, Isabela Dolci, Andre S. Godoy, Jose V. J. Silva Junior, Uriel E. A. Ruiz, Igor A. Santos, Ana C. G. Jardim, Kirandeep Samby, Jeremy N. Burrows, Timothy N. C. Wells, Laura H. V. G. Gil, Glaucius Oliva, Rafaela S. Fernandes
Summary: Chikungunya virus is the causative agent of chikungunya fever, a specific drug against this virus is needed for treatment.
Article
Immunology
Benjamin Mordmueller, Zita Sulyok, Mihaly Sulyok, Zsofia Molnar, Albert Lalremruata, Carlos Lamsfus Calle, Patricia Granados Bayon, Meral Esen, Markus Gmeiner, Jana Held, Henri-Lynn Heimann, Tamirat Gebru Woldearegai, Javier Ibanez, Judith Fluegge, Rolf Fendel, Andrea Kreidenweiss, K. C. Natasha, Tooba Murshedkar, Sumana Chakravarty, Pouria Riyahi, Peter F. Billingsley, L. W. Preston Church, Thomas L. Richie, B. Kim Lee Sim, Stephen L. Hoffman, Peter G. Kremsner
Summary: Immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (SPZ) in PfSPZ Vaccine provides similar protection against controlled human malaria infection (CHMI) with both homologous and heterologous Pf for at least 9-10 weeks.
Article
Pharmacology & Pharmacy
Laura Sibley, Andrew D. White, Charlotte Sarfas, Jennie Gullick, Fergus Gleeson, Faye Lanni, Simon Clark, Emma Rayner, Santiago Ferrer-Bazaga, Fatima Ortega-Muro, Laura Alameda, Joaquin Rullas, Veronica Sousa, Marisa Martinez, Inigo Angulo-Barturen, Adolfo Garcia, Juan Jose Vaquero, Henry E. Pertinez, Geraint Davies, Mike Dennis, Ann Williams, Sally Sharpe
Summary: Innovative cross-over study designs were explored in non-human primate studies to evaluate the effectiveness of drug treatments for tuberculosis. The pharmacokinetics of standard tuberculosis drugs were established in macaques, and two studies were conducted to evaluate the pharmacokinetics and pharmacodynamics of different drug combinations using cross-over designs. The studies supported the utility of the non-human primate model for determining the pharmacokinetics and pharmacodynamics of tuberculosis drugs, but further optimization of cross-over study designs is needed.