Article
Chemistry, Medicinal
Wenbo Yin, Hengxian Cui, Hong Jiang, Yuxin Zhang, Lei Liu, Tianxiao Wu, Yin Sun, Liyu Zhao, Xin Su, Dongmei Zhao, Maosheng Cheng
Summary: The newly synthesized compound 22a exhibited excellent broad-spectrum antifungal activity, showing significant fungicidal activity against multiple susceptible strains and resistant strains, as well as good pharmacokinetic properties.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Wenbo Yin, Yuxin Zhang, Hengxian Cui, Hong Jiang, Lei Liu, Yang Zheng, Tianxiao Wu, Liyu Zhao, Yin Sun, Xin Su, Song Li, Dongmei Zhao, Maosheng Cheng
Summary: A series of novel 5-phenylthiophene derivatives were designed and synthesized to combat fungal infections, with compounds 17b and 17f showing significant antifungal activities. These compounds not only prevented the formation of fungal biofilms, but also displayed satisfactory fungicidal activity against various strains. Compound 17f exhibited potent antifungal activity by inhibiting C. albicans CYP51, and both 17b and 17f were almost non-toxic to mammalian cells, indicating their promise as novel antifungal drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Camila Aparecida da Silva dos Reis Conde, Ana Luiza de Andrade Querino, Heveline Silva, Maribel Navarro
Summary: Cancer is a global public health problem, and there is a demand for better drugs. The repurposing of well-known antifungal agents, such as Clotrimazole and Ketoconazole, as potential anticancer drugs was investigated. Silver(I) complexes derived from these agents showed significant activity against cancer cell lines and had higher selectivity than the free ligands. The potential biological target for the observed anticancer activity was found to be albumin, suggesting its role in transporting/delivering the metal complexes.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Tatsiana V. Tsybruk, Leonid A. Kaluzhskiy, Yuri V. Mezentsev, Tatyana N. Makarieva, Kseniya M. Tabakmaher, Natalia V. Ivanchina, Pavel S. Dmitrenok, Alexander V. Baranovsky, Andrei A. Gilep, Alexis S. Ivanov
Summary: Finding new effective antifungal agents is crucial due to the increasing prevalence of fungal diseases caused by Candida fungi and the development of drug resistance. This study focused on the interaction between C. krusei CYP51 and various ligands, including azole inhibitors and steroid derivatives. The resistance of C. krusei to azoles was found to be a result of a mechanism other than the structural features of CYP51. Promising ligands with strong binding to C. krusei CYP51 were identified, suggesting their potential as selective modulators of this enzyme's activity.
Review
Microbiology
Brian C. Monk, Mikhail Keniya
Summary: Antifungal drugs and agrochemicals are limited by unintended consequences and resistance, highlighting the need for improvement and discovery of novel antifungals. Structural insights into drug targets offer opportunities for more effective antifungal discovery.
Article
Biochemistry & Molecular Biology
L. A. Kaluzhskiy, P. V. Ershov, E. O. Yablokov, Y. V. Mezentsev, O. V. Gnedenko, T. V. Shkel, A. A. Gilep, S. A. Usanov, A. S. Ivanov
Summary: Opportunistic fungi of the genus Candida are major causative agents of mycoses and the development of new antimycotics targeting the cytochrome P450 51 (CYP51) is crucial due to the widespread resistance to azole CYP51 inhibitors. Through bioinformatics analysis, computer molecular modeling, and SPR technology, potential inhibitors from non-azole compounds were identified, showing promising results for the design of new CYP51 inhibitors against Candida fungi.
BIOCHEMISTRY MOSCOW-SUPPLEMENT SERIES B-BIOMEDICAL CHEMISTRY
(2021)
Review
Chemistry, Organic
Parteek Prasher, Mousmee Sharma, Flavia Zacconi, Gaurav Gupta, Alaa A. A. Aljabali, Vijay Mishra, Murtaza M. Tambuwala, Deepak N. Kapoor, Poonam Negi, Terezinha de Jesus Andreoli Pinto, Inderbir Singh, Dinesh K. Chellappan, Kamal Dua
Summary: Azole frameworks play a crucial role in drug design, facilitating the development of highly selective and physiological-friendly chemotherapeutics, as well as tailored therapeutics. They are integral in advanced drug design methods, aiding in rapid identification of active molecules and optimization of drug molecules.
CURRENT ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Wei-Chung Chiou, Meng-Shiuan Hsu, Yun-Ti Chen, Jinn-Moon Yang, Yeou-Guang Tsay, Hsiu-Chen Huang, Cheng Huang
Summary: Researchers have identified several FDA-approved drugs that can effectively inhibit the proteolytic activity of SARS-CoV-2 virus, demonstrating their therapeutic potential for treating COVID-19 and other Betacoronavirus infections.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Francesco Morra, Francesco Merolla, Giovanna Damia, Francesca Ricci, Silvia Varricchio, Gennaro Ilardi, Laura Arenare, Daniela Califano, Virginia Napolitano, Robert Fruscio, Rosa Marina Melillo, Luca Palazzo, Angela Celetti
Summary: This study reveals that the physical or functional loss of CCDC6 enhances the activity of the PP4c complex, resulting in PARPi sensitivity. Moreover, downregulation of CCDC6 may overcome PARPi resistance in HGSOCs.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Biology
Vasundara Srinivasan, Hevila Brognaro, Prince R. Prabhu, Edmarcia Elisa de Souza, Sebastian Guenther, Patrick Y. A. Reinke, Thomas J. Lane, Helen Ginn, Huijong Han, Wiebke Ewert, Janina Sprenger, Faisal H. M. Koua, Sven Falke, Nadine Werner, Hina Andaleeb, Najeeb Ullah, Bruno Alves Franca, Mengying Wang, Angelica Luana C. Barra, Markus Perbandt, Martin Schwinzer, Christina Schmidt, Lea Brings, Kristina Lorenzen, Robin Schubert, Rafael Rahal Guaragna Machado, Erika Donizette Candido, Danielle Bruna Leal Oliveira, Edison Luiz Durigon, Stephan Niebling, Angelica Struve Garcia, Oleksandr Yefanov, Julia Lieske, Luca Gelisio, Martin Domaracky, Philipp Middendorf, Michael Groessler, Fabian Trost, Marina Galchenkova, Aida Rahmani Mashhour, Sofiane Saouane, Johanna Hakanpaeae, Markus Wolf, Maria Garcia Alai, Dusan Turk, Arwen R. Pearson, Henry N. Chapman, Winfried Hinrichs, Carsten Wrenger, Alke Meents, Christian Betzel
Summary: Three natural phenolic compounds have been found to bind to an allosteric site in SARS-CoV-2 papain-like protease, displaying antiviral activity in vitro and showing potential as starting scaffolds for drug design. These compounds can prevent essential molecular interactions and reinstate the host's antiviral immune response that is down-regulated in COVID-19 infections.
COMMUNICATIONS BIOLOGY
(2022)
Review
Oncology
Elsa Maitre, Jerome Paillassa, Xavier Troussard
Summary: This article discusses different diseases in the category of mature B-cell neoplasms, such as HCL, SMZL, SDRPL, and SBLPN, and mentions the mutations and signaling pathways associated with these diseases, as well as introduces some new targeted therapies.
FRONTIERS IN ONCOLOGY
(2022)
Review
Pharmacology & Pharmacy
Leila Mousavifar, Rene Roy
Summary: Glycomimetics that mimic complex carbohydrate structures show potential in pathological processes and combatting antibiotic-resistant Escherichia coli infections. Advances in the synthesis of this compound family have been made, with one already in clinical trials for treating Crohn's disease, offering new hope for alternative antibacterial strategies.
DRUG DISCOVERY TODAY
(2021)
Article
Biochemistry & Molecular Biology
Alexander M. Andrianov, Yuri V. Kornoushenko, Anna D. Karpenko, Ivan P. Bosko, Alexander V. Tuzikov
Summary: A computational approach was used to identify small drug-like compounds mimicking X77 for SARS-CoV-2 M-Pro inhibition. Five top-ranking compounds with high binding affinity to M-Pro were predicted, showing potential as scaffolds for novel antiviral agents targeting the active site of SARS-CoV-2 M-Pro.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Endocrinology & Metabolism
Marta Baviera, Stefano Genovese, Vito Lepore, Pierluca Colacioppo, Fabio Robusto, Mauro Tettamanti, Antonio D'Ettorre, Fausto Avanzini, Ida Fortino, Antonio Nicolucci, Maria C. Roncaglioni, Francesco Giorgino
Summary: This observational cohort study in Italy compared the efficacy and safety of GLP-1RAs and SGLT2 inhibitors with other AHAs in large and unselected populations. The findings showed that GLP-1RAs and SGLT2 inhibitors were associated with lower rates of death, cardiovascular events, and heart failure compared to other AHAs, indicating their favorable effects in type 2 diabetes patients beyond those with cardiovascular disease.
DIABETES OBESITY & METABOLISM
(2021)
Article
Oncology
Harish Kumar, Suman Mazumder, Neeraj Sharma, Sayak Chakravarti, Mark D. Long, Nathalie Meurice, Joachim Petit, Song Liu, Marta Chesi, Sabyasachi Sanyal, A. Keith Stewart, Shaji Kumar, Leif Bergsagel, S. Vincent Rajkumar, Linda B. Baughn, Brian G. Van Ness, Amit Kumar Mitra
Summary: This study demonstrates that clofazimine (CLF) has significant cytotoxicity against drug-resistant multiple myeloma (MM) as a single agent and in combination with proteasome inhibitors (PIs) and immunomodulatory derivatives (IMiDs). CLF induces multiple cell death pathways and effectively kills myeloma stem-like cells. With its FDA approval, high safety profile, and low cost, CLF has the potential to be repurposed rapidly as a safe and cost-effective anti-myeloma drug.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Simone Giovannuzzi, Chad S. Hewitt, Alessio Nocentini, Clemente Capasso, Gabriele Costantino, Daniel P. Flaherty, Claudiu T. Supuran
Summary: The inhibition of alpha-class carbonic anhydrases (CAs) from bacterial pathogens by phenols and phenolic acids was investigated. Small changes in the phenol scaffold led to drastic effects on the inhibitory activity of bacterial CA. This underinvestigated class of bacterial CA inhibitors may have potential in fighting drug resistant bacteria.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Mariagrazia Rullo, Marco Cipolloni, Marco Catto, Carolina Colliva, Daniela Valeria Miniero, Tiziana Latronico, Modesto de Candia, Tiziana Benicchi, Anna Linusson, Nicola Giacche, Cosimo Damiano Altomare, Leonardo Pisani
Summary: In this study, bioisosteric replacements of important functional groups (H/F and CH2OH/CF2H) in coumarin derivatives were investigated to explore their effects on inhibitory potency and drug-likeness. The results showed that compound 15 exhibited strong inhibitory activities against both AChE and MAO B, along with good water solubility and oral bioavailability. It has the potential to be a neuroprotective agent.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Damiano Tanini, Antonella Capperucci, Maria Locuoco, Marta Ferraroni, Gabriele Costantino, Andrea Angeli, Claudiu T. Supuran
Summary: A series of benzoselenoates were prepared and investigated for their inhibitory properties against various human Carbonic Anhydrases isoforms. The study revealed that benzoselenoates may serve as potential new inhibitors with higher selectivity and efficacy for different hCAs.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Andrea Angeli, Marta Ferraroni, Antonella Capperucci, Damiano Tanini, Gabriele Costantino, Claudiu T. Supuran
Summary: This study presents the activity of selenocarbamates as novel carbonic anhydrase (CA) inhibitors. Through CA-mediated hydrolysis, selenocarbamates release selenolates that effectively inhibit CA by binding to zinc. Different human CA isoforms were evaluated against a series of selenocarbamates with high molecular diversity and complexity. X-ray studies provided insights into the binding mode of this novel class of CA inhibitors.
Article
Biochemistry & Molecular Biology
Andrea Mammoli, Elisa Bianconi, Luana Ruta, Alessandra Riccio, Carlo Bigiotti, Maria Souma, Andrea Carotti, Sofia Rossini, Chiara Suvieri, Maria Teresa Pallotta, Ursula Grohmann, Emidio Camaioni, Antonio Macchiarulo
Summary: Over the last two decades, IDO1 has been recognized as a crucial player in immune regulation. This study presents a screening campaign of a compound fragment library and discusses the impact of IDO1's structural plasticity on drug design.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Andrea Angeli, Marta Ferraroni, Fabrizio Carta, Cecile Haeberli, Jennifer Keiser, Gabriele Costantino, Claudiu T. Supuran
Summary: The limited options for treating schistosomiasis necessitate the discovery of alternative drugs. This study successfully inhibited the growth of Schistosoma mansoni using new PZQ derivatives, but further optimization is still needed.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Pilar Maria Luque-Navarro, Elena Mariotto, Marco Ballarotto, Gianluca Rubbini, Francisco Jose Aguilar-Troyano, Alberto Fasiolo, Archimede Torretta, Emilio Parisini, Antonio Macchiarulo, Alejandro Laso, Carmen Marco, Giampietro Viola, Maria Paz Carrasco-Jimenez, Luisa Carlota Lopez-Cara
Summary: This study presents a series of compounds designed based on a known strategy. Some of these compounds show improved enzyme inhibition and antiproliferative effects, with Ff-35 being the most promising compound that inhibits the growth of different tumor cells and induces cell cycle arrest and apoptosis.
Article
Chemistry, Medicinal
Silvia Grottelli, Giannamaria Annunziato, Gioena Pampalone, Marco Pieroni, Mirco Dindo, Francesca Ferlenghi, Gabriele Costantino, Barbara Cellini
Summary: This study aimed to find pharmacological chaperones for the treatment of primary hyperoxaluria type I (PH1). The researchers screened and chemically optimized compounds, identifying a promising hit compound and drawing conclusions about the requirements for optimal pharmacological chaperone activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Filippo Pigazzani, Davide Gorni, Kenneth A. Dyar, Matteo Pedrelli, Gwen Kennedy, Gabriele Costantino, Agostino Bruno, Isla Mackenzie, Thomas M. MacDonald, Uwe J. F. Tietge, Jacob George
Summary: Oxidative stress plays a role in the development and exacerbation of cardiovascular diseases. Derivatives-reactive oxygen metabolites (d-ROMs) are a new biomarker of oxidative stress that can be quantified within minutes. High levels of d-ROMs are an independent predictor of cardiovascular events and mortality, while low levels of d-ROMs are a good negative predictor for cardiovascular events in patients with coronary artery disease and heart failure. Combining d-ROMs with other commonly used biomarkers may help in more accurate cardiovascular risk assessment.
Article
Microbiology
Anna Gidari, Samuele Sabbatini, Elisabetta Schiaroli, Sabrina Bastianelli, Sara Pierucci, Chiara Busti, Lucia Comez, Valeria Libera, Antonio Macchiarulo, Alessandro Paciaroni, Ilaria Vicenti, Maurizio Zazzi, Daniela Francisci
Summary: This study investigated the activity of molnupiravir in combination with nirmatrelvir or GC376 on SARS-CoV-2. The results showed that molnupiravir and GC376 exhibited synergistic activity at 48 hours and additive activity at 72 hours. Molnupiravir and nirmatrelvir exhibited synergistic activity at both 48 hours and 72 hours.
Article
Chemistry, Medicinal
Gustavo Provensi, Alessia Costa, Barbara Rani, Maria Vittoria Becagli, Fabio Vaiano, Maria Beatrice Passani, Damiano Tanini, Antonella Capperucci, Simone Carradori, Jacobus P. Petzer, Anel Petzer, Daniela Vullo, Gabriele Costantino, Patrizio Blandina, Andrea Angeli, Claudiu T. Supuran
Summary: This study reported the synthesis of β-arylchalcogeno amines with structural similarity to amphetamine, which showed good activation properties for certain enzymes in the brain. In vivo evaluation demonstrated the procognitive effects of these compounds without causing unwanted side effects. These findings suggest the potential utility of these compounds for improving cognitive decline associated with neurodegenerative and psychiatric diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Miriam Girardini, Francesca Ferlenghi, Giannamaria Annunziato, Giulia Degiacomi, Bianca Papotti, Cinzia Marchi, Jose Camilla Sammartino, Sari S. Rasheed, Anna Contini, Maria Rosalia Pasca, Federica Vacondio, Joanna C. Evans, Thomas Dick, Rolf Mueller, Gabriele Costantino, Marco Pieroni
Summary: Tuberculosis is a deadly infectious disease and the increase in drug-resistant strains is concerning. Previous studies have identified compounds with inhibitory activity against Mycobacterium tuberculosis strains. In this study, researchers aimed to determine the metabolic fate of these compounds and explore structural modifications to improve activity and avoid rapid clearance. Novel antitubercular chemotypes were also investigated. The findings led to the design of improved compounds with good activity against drug-susceptible and drug-resistant strains.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ina Varfaj, Andrea Carotti, Luciano Mangiapelo, Lina Cossignani, Agnese Taticchi, Antonio Macchiarulo, Federica Ianni, Roccaldo Sardella
Summary: Two LC methods were developed for the analysis of achiral and chiral components of amino acids in a food supplement. Both methods performed well for all eight amino acids, confirming the consistency of amino acid content with manufacturer's declaration. Additionally, a two-dimensional achiral-chiral configuration was proven to be possible in practice, making the methods more environmentally sustainable.
Article
Biochemistry & Molecular Biology
Alessandro Paciaroni, Valeria Libera, Francesca Ripanti, Andrea Orecchini, Caterina Petrillo, Daniela Francisci, Elisabetta Schiaroli, Samuele Sabbatini, Anna Gidari, Elisa Bianconi, Antonio Macchiarulo, Rohanah Hussain, Lucia Silvestrini, Paolo Moretti, Norhan Belhaj, Matteo Vercelli, Yessica Roque, Paolo Mariani, Lucia Comez, Francesco Spinozzi
Summary: The main protease (Mpro) is a conserved enzyme among coronaviruses and is a potential target for developing drugs against coronaviruses. GC376 and Nirmatrelvir (NMV) can bind strongly to SARS-CoV-2 Mpro and stabilize the dimeric state, inhibiting its activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Marialaura Pavone, Samanta Raboni, Marialaura Marchetti, Giannamaria Annunziato, Stefano Bettati, Bianca Papotti, Cinzia Marchi, Emanuele Carosati, Marco Pieroni, Barbara Campanini, Gabriele Costantino
Summary: The development of antibiotic adjuvants as inhibitors of non-essential targets is an innovative approach to combat antimicrobial resistance. This study focuses on compounds targeting serine acetyltransferase (SAT), a key enzyme involved in cysteine biosynthesis. A new compound with promising SAT inhibitory activity has been discovered, and further investigation into its potential and structure-activity relationships has been conducted.
RESULTS IN CHEMISTRY
(2022)