Review
Oncology
Massimo Serra, Davide Rubes, Sergio Schinelli, Mayra Paolillo, Deborah Lannigan
Summary: Metastasis is the main reason for the failure of anti-cancer therapy and has a negative impact on patient prognosis. The development of efficient therapeutic strategies targeting key targets in the metastatic process is crucial to prolong cancer patient survival and make cancer a manageable chronic disease. Traditional chemotherapy has limited efficacy against metastatic cells due to the selection of chemo-resistant cell populations undergoing epithelial-to-mesenchymal transition (EMT), leading to colonization of distant sites and sustaining the metastatic process.
Review
Biochemistry & Molecular Biology
Vanktesh Kumar, Navjot Kaur, Sanjeev Sahu, Vikas Sharma, Deepak Kumar, Ajit Sharma, Pankaj Wadhwa
Summary: Cancer is a non-communicable disease with increasing cases and higher morbidity and mortality rates globally. Tyrosine kinase has been identified as an important target for anticancer therapy, and this review summarizes potent molecules that act against tyrosine kinases.
CURRENT MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Giambattista Marotta, Filippo Basagni, Michela Rosini, Anna Minarini
Summary: Fyn kinase plays crucial roles in cell signaling pathways, involved in various biological functions in cancer and the nervous system. Research on Fyn inhibitors has made significant progress and offers promising opportunities for therapeutic intervention in neurodegenerative diseases.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Stefania Demuro, Conall Sauvey, Shailesh K. Tripathi, Rita M. C. Di Martino, Da Shi, Jose A. Ortega, Debora Russo, Beatrice Balboni, Barbara Giabbai, Paola Storici, Stefania Girotto, Ruben Abagyan, Andrea Cavalli
Summary: The human kinome plays a crucial role in various pathways and its dysregulation is associated with central nervous system-related disorders. Simultaneously modulating multiple protein kinases through pharmacological approaches may lead to superior therapeutic effects compared to traditional single target, single drug approaches.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Sandra Roehm, Benedict-Tilman Berger, Martin Schroeder, Deep Chatterjee, Sebastian Mathea, Andreas C. Joerger, Daniel M. Pinkas, Joshua C. Bufton, Amelie Tjaden, Lohitesh Kovooru, Mark Kudolo, Christian Pohl, Alex N. Bullock, Susanne Mueller, Stefan Laufer, Stefan Knapp
Summary: In this study, a potent and cell-active dual DDR/p38 chemical probe was developed, along with a structurally related negative control, for studying DDR kinase signaling. The structure-guided design approach provided insights into the folding process of p38 and how non-conserved amino acids modulate inhibitor selectivity. The developed DDR/p38 probe is a valuable tool for investigating the role of DDR kinase in normal physiology and disease development.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Francesca Quartieri, Marcella Nesi, Nilla R. Avanzi, Daniela Borghi, Elena Casale, Emiliana Corti, Ulisse Cucchi, Daniele Donati, Marina Fasolini, Eduard R. Felder, Arturo Galvani, Maria L. Giorgini, Antonio Lomolino, Maria Menichincheri, Christian Orrenius, Claudia Perrera, Stefania Re Depaolini, Federico Riccardi-Sirtori, Enea Salsi, Antonella Isacchi, Paola Gnocchi
Summary: This article describes the identification of unprecedented ATP-competitive ChoK alpha inhibitors starting from an initial hit NMS-P830. The structure-based medicinal chemistry program resulted in the discovery of selective compounds with good biochemical activity, solubility, and metabolic stability, suitable for further optimization. The ChoK alpha inhibitors disclosed in this study are the first to demonstrate the potential for inhibiting ChoK alpha with ATP-competitive compounds.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Qianqian Shi, Huiqi Wen, Yijie Xu, Xu Zhao, Jing Zhang, Ye Li, Qingbin Meng, Fang Yu, Junhai Xiao, Xingzhou Li
Summary: This study focused on the role of LsrK and its potential as a target for Quorum Sensing Inhibitors (QSIs). Through various methods including molecular dynamics simulation, virtual screening, and laboratory assays, several potential LsrK kinase inhibitors were identified. Four compounds were found to effectively inhibit LsrK activity, and two of them were confirmed to specifically bind to LsrK. This research provides valuable insights for the discovery of QSIs that can avoid the emergence of drug resistance.
FRONTIERS IN CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Taylor K. Johnson, Daniel A. Bochar, Nathalie M. Vandecan, Jessica Furtado, Michael P. Agius, Sameer Phadke, Matthew B. Soellner
Summary: The study suggests that ATP-competitive inhibitors and allosteric inhibitors of Abl kinase do not exhibit synergy, but conformation-selective ATP-site inhibitors can have synergy with allosteric ABL inhibitors. The key driver for simultaneously binding two compounds to Abl kinase is the kinase conformation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Aysha Gaur, Mudasir Nabi Peerzada, Nashrah Sharif Khan, Imran Ali, Amir Azam
Summary: A series of novel indole based sulfonohydrazide derivatives containing morpholine heterocyclic ring were synthesized and evaluated for their anticancer activity. Compound 5f showed promising inhibition of breast cancer cells and was found to be non-toxic to noncancerous cells.
Article
Multidisciplinary Sciences
Daniel Paprocki, Maria Winiewska-Szajewska, Elzbieta Speina, Roza Kucharczyk, Jaroslaw Poznanski
Summary: The study found that iodinated compounds are an attractive alternative to brominated ones, with one of the new iodinated compounds showing superior performance in terms of cytotoxicity and mitochondrial activity, becoming a candidate leader in the further development of CK2 inhibitors.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Multidisciplinary
Xue Lou, Hui Wang, Yu Liu, Yongwei Huang, Zhonghua Liu, Wei Zhang, Tie Wang
Summary: This study presents a perylene monoamide-based reactive oxygen species supergenerator that induces oxidative stress and triggers immunogenic cell death, leading to efficient tumor therapy. It also demonstrates the potential of perylene as a therapeutic platform for immunogenic photochemotherapy against hypoxic tumors.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Pharmacology & Pharmacy
Charu Chaudhry, Andrew Tebben, S. John Tokarski, Robert Borzilleri, J. William Pitts, Jonathan Lippy, Litao Zhang
Summary: Kinases, which account for 20% of the human genome, have been a major focus in pharmaceutical drug discovery for over three decades. Despite the challenges in identifying novel kinase inhibitors with good properties, the need for diverse and powerful tools in kinase drug discovery is evident in order to efficiently generate highly optimized kinase inhibitors.
DRUG DISCOVERY TODAY
(2021)
Article
Multidisciplinary Sciences
James Knockleby, Aicha Dede Djigo, Indeewari Kalhari Lindamulage, Chandrabose Karthikeyan, Piyush Trivedi, Hoyun Lee
Summary: Compounds targeting tubulin as potential anticancer agents have shown promising efficacy and safety, with CTR-21 and CTR-32 identified as lead compounds that effectively kill a variety of cancer cells, including multi-drug resistant cells, and exhibit high selectivity against cancer cells. These compounds prevent tubulin polymerization and induce cell cycle arrest at G2/M, with CTR-21 demonstrating more favorable metabolic properties and showing synergistic effects when combined with the Bcl-2 inhibitor ABT-737.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Kyu Ri Hahn, Hyun Jung Kwon, Yeo Sung Yoon, Dae Won Kim, In Koo Hwang
Summary: In this study, a fusion protein PEP-1-PGK1 was synthesized that can cross the blood-brain barrier, and it was found that low concentrations of PEP-1-PGK1 can prevent neuronal stress and ischemia-related damage.
Review
Pharmacology & Pharmacy
Yazan Haddad, Marek Remes, Vojtech Adam, Zbynek Heger
Summary: The study utilized variations in 110 crystal structures to assemble eight distinct families highlighting the C-helix orientation in the N-lobe of the EGFR kinase domain. These families shared similar mutational profiles, ligand R-groups facing the C-helix, mutation sites, and DFG domain.
DRUG DISCOVERY TODAY
(2021)
Article
Biochemistry & Molecular Biology
Claudia Ardino, Filomena Sannio, Carolina Pasero, Lorenzo Botta, Elena Dreassi, Jean-Denis Docquier, Ilaria D'Agostino
Summary: Trifluoroacetic acid (TFA) is commonly used in synthetic strategies due to its strong acidity and low boiling point. However, residual amounts of TFA may affect the accuracy of cellular assays. This study evaluates the effect of different counterions on the biological activity of an antibacterial compound and optimizes the preparation methods.
MOLECULAR DIVERSITY
(2023)
Review
Chemistry, Organic
Maria Grazia Martina, Lisa Giannessi, Marco Radi
Summary: It is widely recognized that the building blocks of life, purines and pyrimidines, were created through multicomponent reactions on early abiotic Earth. These structures evolved into biologically relevant molecules and served as templates for drug development. The synthetic community has dedicated efforts to replicate the abiotic synthesis of purines and pyrimidines, resulting in the development of various multicomponent synthesis methods. The importance of multicomponent synthesis of new heterocycles is highlighted by the shift towards green chemistry and pharmaceutical sustainability. This review provides an overview of the most important multicomponent approaches for synthesizing purine and pyrimidine derivatives for potential pharmacological applications.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Annalaura Brai, Federica Poggialini, Chiara Vagaggini, Claudia Pasqualini, Sauro Simoni, Valeria Francardi, Elena Dreassi
Summary: A novel, cheap and convenient toxicity model using Tenebrio molitor coleoptera (TMC) was developed for preliminary evaluation of drug safety and metabolite formation. The results demonstrate that TMC can be used as a preliminary toxicity model to assess the safety of experimental compounds and the formation of main metabolites, and to reduce the costs and number of rodents, according to 3R principles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Federica Poggialini, Chiara Vagaggini, Annalaura Brai, Claudia Pasqualini, Emmanuele Crespan, Giovanni Maga, Cecilia Perini, Noemi Cabella, Lorenzo Botta, Francesca Musumeci, Maria Frosini, Silvia Schenone, Elena Dreassi
Summary: In this study, a series of pyrazolo[3,4-d]pyrimidine derivatives from an in-house library were evaluated for their potential as therapeutic candidates against glioblastoma. Compound 5 demonstrated promising inhibitory activity against c-Src and Abl, significant antiproliferative effects on GBM cell lines, and low toxicity towards healthy cells. These findings highlight compound 5 as a potential treatment for further in vivo assays.
Article
Agriculture, Multidisciplinary
A. Brai, C. Vagaggini, C. Pasqualini, F. Poggialini, F. Tarchi, V. Francardi, E. Dreassi
Summary: This study demonstrates that distillery by-products contain abundant antioxidant compounds and beneficial fatty acids even after processing. Using them as feed for Tenebrio molitor larvae not only increases the average weight gain of the larvae but also has no effect on their survival rate. Furthermore, the use of these by-products can enhance the total antioxidant activity and improve the nutraceutical properties of the larvae.
JOURNAL OF INSECTS AS FOOD AND FEED
(2023)
Article
Agriculture, Multidisciplinary
A. Brai, F. Poggialini, C. I. Trivisani, C. Vagaggini, F. Tarchi, V. Francardi, E. Dreassi
Summary: Circular economy principles combined with the search for novel sustainable functional foods can transform agricultural waste into feed supplements, creating benefits for the environment, industries, and consumers. The study found that using tomato peels and seeds, olive and mastic leaves as feed supplements efficiently supported the growth of Tenebrio molitor larvae, increased antioxidant activities, and improved fatty acid composition.
JOURNAL OF INSECTS AS FOOD AND FEED
(2023)
Article
Chemistry, Medicinal
Maria Grazia Martina, Federica Giammarino, Ilaria Vicenti, Elisabetta Groaz, Jef Rozenski, Matteo Incerti, Filomena Sannio, Jean Denis Docquier, Maurizio Zazzi, Marco Radi
Summary: The increasing number of viral outbreaks in recent years calls for the development of novel broad-spectrum antivirals. Non-natural nucleosides have shown to be successful in treating infectious diseases and new base-modified nucleosides were developed for potential antimicrobial activity against different viruses and bacteria.
Article
Pharmacology & Pharmacy
Marika Allodi, Carmine Giorgio, Matteo Incerti, Domenico Corradi, Lisa Flammini, Vigilio Ballabeni, Elisabetta Barocelli, Marco Radi, Simona Bertoni
Summary: This study aims to further investigate the effects of MR120 on chronic colitis and evaluate its anti-inflammatory effect on a mouse model of chronic colitis induced by DSS. The results showed that MR120 significantly improved the health conditions of the mice and attenuated multiple systemic and local inflammatory responses caused by inflammation. Although more potent analogues are needed for clinical translation, this study provides valuable evidence of the in vivo efficacy of CCL20/CCR6 modulators in a chronic model of IBD.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chiara Compagnoni, Roberta Capelli, Veronica Zelli, Alessandra Corrente, Davide Vecchiotti, Irene Flati, Mauro Di Vito Nolfi, Adriano Angelucci, Edoardo Alesse, Francesca Zazzeroni, Alessandra Tessitore
Summary: This study aimed to explore the expression levels and functional relationships between miR-182-5p and Cyld-Foxo1 in hepatic tissues from a diet-induced NAFLD/HCC mouse model. The results showed that miR-182-5p was upregulated during NAFLD progression and in tumors, and it inhibited the expression of tumor-suppressor genes Cyld and Foxo1 in HepG2 cells. Analysis of human HCC samples confirmed these findings and demonstrated the potential of miR-182-5p as a diagnostic biomarker or therapeutic target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Annalaura Brai, Federica Poggialini, Claudia Pasqualini, Claudia Immacolata Trivisani, Chiara Vagaggini, Elena Dreassi
Summary: Vaccines are crucial for preventing pathogen diffusion and cancer. The addition of adjuvants enhances the immune response to antigens, improving the effectiveness and duration of protection. The search for new adjuvants has increased in recent decades, uncovering novel classes and mechanisms of action, but there is still much to learn.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Lorenzo Jacopo Ilic Balestri, Claudia Immacolata Trivisani, Francesco Orofino, Diego Fiorucci, Giuseppina Ivana Truglio, Ilaria D'Agostino, Federica Poggialini, Lorenzo Botta, Jean-Denis Docquier, Elena Dreassi
Summary: Our research group has been studying the development of macrocyclic amidinoureas (MCAs) as antifungal agents. Through in silico target fishing study, we identified chitinases as one of their potential targets. Compound 3f emerged as a promising inhibitor of acidic mammalian chitinase (AMCase) with improved potency and selectivity.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Carmela Mazzoccoli, Fabiana Crispo, Ilaria Laurenzana, Michele Pietrafesa, Lorenza Sisinni, Rosa Lerose, Donatella Telesca, Maria R. Milella, Te Liu, Gerardo Della Sala, Jessica Sebastiani, Romano Silvestri, Giuseppe La Regina
Summary: This study investigates the molecular mechanisms of a new tubulin inhibitor, ARDAP, and finds that it can effectively treat solid tumors by inhibiting cell proliferation and metastasis, as well as promoting cell differentiation. ARDAP exhibits low toxicity towards breast cancer cells and no significant harm to healthy cells, making it a promising candidate for chemotherapy or adjuvant therapy.
ARCHIV DER PHARMAZIE
(2023)
Article
Chemistry, Medicinal
Irene Brusa, Elvira Sondo, Emanuela Pesce, Valeria Tomati, Dario Gioia, Federico Falchi, Beatrice Balboni, Jose Antonio Ortega Martinez, Marina Veronesi, Elisa Romeo, Natasha Margaroli, Maurizio Recanatini, Stefania Girotto, Nicoletta Pedemonte, Marinella Roberti, Andrea Cavalli
Summary: A new RNF5 inhibitor, called 1,2,4-thiadiazol-5-ylidene, has been discovered in this study. It selectively corrects the folding defect of CFTR protein in CF patients and has no toxic side effects. This finding provides evidence for the pursuit of novel treatment strategies for CF.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Chiara Vagaggini, Annalaura Brai, Denise Bonente, Jessica Lombardi, Federica Poggialini, Claudia Pasqualini, Virginia Barone, Claudio Nicoletti, Eugenio Bertelli, Elena Dreassi
Summary: In this study, a sensitive and reproducible LC-MS/MS method was developed and validated for the quantification of short-chain fatty acids (SCFAs) in human, rat, and mouse plasma. The method showed good performance in terms of recovery (> 80%), precision (RSD <14%), accuracy (RE < ± 10%), and sensitivity (LOQ of 0.01 μM for acetic, butyric, propionic, and isobutyric acid). The results highlighted the correlation between plasma concentrations of SCFAs and age, emphasizing the importance of developing a reliable method for their quantification to study their biological role.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Biochemistry & Molecular Biology
Marisanna Centini, Isabel Martinez-Sanudo, Marco Biagi, Elena Dreassi, Luca Mazzon, Laura Marri
Summary: In recent years, the use of bacteria for carotenoid production has gained attention as a sustainable alternative to expensive and technically challenging chemical synthesis. This study reports the isolation of an orange-pigmented bacterium from the gut of adult olive flies, contributing to the repertoire of carotenogenic bacteria. The isolated bacterium, designated as M3d10, was found to be a derivative of hydroxylated astaxanthin through preliminary characterization.