Article
Biochemistry & Molecular Biology
Hisham A. Elrufaie, Linda M. Mohamed, Aya Y. Hamd, Noor A. Bala, Fatima A. Elbadawi, Hiba Ghaboosh, Abdulrahim A. Alzain
Summary: This study used computational methods to identify natural products that inhibit the parasitic enzyme Rhodesain. Three potential compounds were found, which showed excellent binding affinity and stability towards Rhodesain. These compounds may be a hopeful treatment for Human African Trypanosomiasis (HAT) in the future if further clinical trials were conducted.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Baljinder Singh, Amrita Sharma, Naresh Gunaganti, Mitch Rivers, Pradip K. Gadekar, Brady Greene, Michael Chichioco, Carlos E. Sanz-Rodriguez, Courtney Fu, Catherine LeBlanc, Erin Burchfield, Nyle Sharif, Benjamin Hoffman, Gaurav Kumar, Andrei Purmal, Kojo Mensa-Wilmot, Michael P. Pollastri
Summary: New analogs of the carbazole CBL0137 were synthesized and evaluated, resulting in the discovery of eight compounds with higher or equivalent selectivity indices. Among them, 5v demonstrated potential for drug development against human African trypanosomiasis (HAT), while 5w showed lack of efficacy. Lessons from these studies will guide further optimization of carbazoles for HAT and other indications.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Baljinder Singh, Amrita Sharma, Naresh Gunaganti, Mitch Rivers, Pradip K. Gadekar, Brady Greene, Michael Chichioco, Carlos E. Sanz-Rodriguez, Courtney Fu, Catherine LeBlanc, Erin Burchfield, Nyle Sharif, Benjamin Hoffman, Gaurav Kumar, Andrei Purmal, Kojo Mensa-Wilmot, Michael P. Pollastri
Summary: To develop a candidate drug against human African trypanosomiasis (HAT), researchers synthesized new analogs and evaluated their properties. Eight new compounds with higher or equivalent selectivity indices were identified. Two compounds, 5v and 5w, were tested in a mouse model of HAT, and 5v showed a lead-like profile for drug development while 5w lacked efficacy. These findings will guide further optimization of carbazoles for HAT and other indications.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Igor Jose dos Santos Nascimento, Thiago Mendonca de Aquino, Edeildo Ferreira da Silva-Junior
Summary: This review discusses the development of cruzain and rhodesain inhibitors in the past 10 years, which could serve as a basis for the discovery of new trypanocidal drugs in the future.118 studies on inhibitors of cruzain and rhodesain were identified, indicating the potential for developing new treatments against Chagas disease and sleeping sickness.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Alkeiver S. Cannon, Prakash S. Nagarkatti, Mitzi Nagarkatti
Summary: Activation of Aryl Hydrocarbon Receptor (AhR) was previously excluded from therapeutic approaches due to potential toxic effects and induction of Cyp1a1 enzyme. However, it is now understood that AhR activation functions as an environmental sensor and immunomodulator, attenuating inflammation. This review summarizes research on AhR and its role in regulating inflammation, highlighting its potential in immune response modulation for inflammatory and autoimmune diseases. The opportunities and challenges of developing AhR-based therapies to suppress inflammation are also discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
William J. Robinson, Annie E. Taylor, Solange Lauga-Cami, George W. Weaver, Randolph Rj Arroo, Marcel Kaiser, Sheraz Gul, Maria Kuzikov, Bernhard Ellinger, Kuldip Singh, Tanja Schirmeister, Adolfo Botana, Chatchakorn Eurtivong, Avninder S. Bhambra
Summary: Human African trypanosomiasis, or sleeping sickness, is a neglected tropical disease caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense, with current therapy limitations and the need for further investigation. Novel anti-trypanosomal compounds show promising potential, providing scaffolds for future drug development targeting the disease.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Ammar Usman Danazumi, Ibtida Tabassum Ishmam, Salisu Idris, Matylda Anna Izert, Emmanuel Oluwadare Balogun, Maria Wiktoria Gorna
Summary: African trypanosomiasis is a fatal disease prevalent in sub-Saharan African countries, caused by infection with African trypanosomes transmitted by haematophagous insects. Current treatments are ineffective and toxic, so there is a need to explore novel methods like proteolysis-targeting chimeras (PROTACs) for drug discovery.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Chatchakorn Eurtivong, Collin Zimmer, Tanja Schirmeister, Chutikarn Butkinaree, Rungroj Saruengkhanphasit, Worawat Niwetmarin, Somsak Ruchirawat, Avninder S. S. Bhambra
Summary: A virtual screening of a ChemBridge molecule collection identified two nitrogenous heterocyclic molecules (12 and 15) with potential dual inhibitory properties against trypanosomal cruzain and rhodesain cysteine proteases. Molecular dynamics simulations revealed that the molecules can occupy the binding sites and stabilize the protease complexes. Binding affinity calculations showed that the virtual hits have comparable affinities to other known inhibitors, making them promising scaffolds with dual inhibition properties.
MOLECULAR DIVERSITY
(2023)
Article
Biochemical Research Methods
Maryam Aliee, Matt J. Keeling, Kat S. Rock
Summary: This study investigates the role of asymptomatic infections in the elimination of Gambiense African sleeping sickness transmission, showing that these infections may significantly impact transmission and hinder progress towards achieving elimination goals. Location-specific modeling and research are needed to determine if asymptomatic infections pose a threat.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Santo Previti, Roberta Ettari, Carla Di Chio, Rahul Ravichandran, Marta Bogacz, Ute A. Hellmich, Tanja Schirmeister, Sandro Cosconati, Maria Zappala
Summary: Human African Trypanosomiasis (HAT) is a challenging parasitic disease and the development of effective drugs remains a challenge. In this study, a series of molecules targeting the main cysteine protease of T. b. rhodesiense were synthesized and evaluated. The results showed promising activity and selectivity against the protozoa, suggesting these molecules could be potential anti-HAT agents for further investigation.
Article
Pharmacology & Pharmacy
Antoine Tarral, Lionel Hovsepian, Thierry Duvauchelle, Yves Donazzolo, Mathilde Latreille, Mathieu Felices, Virginie Gualano, Sophie Delhomme, Olaf Valverde Mordt, Severine Blesson, Pascal Voiriot, Nathalie Strub-Wourgaft
Summary: This study determined the best dose regimen for Acoziborole, a novel boron-containing drug for the treatment of HAT. The drug was well tolerated at all tested doses and had a long duration of action. The findings suggest that Acoziborole could potentially be used as a single-dose oral cure for both stages of HAT.
CLINICAL PHARMACOKINETICS
(2023)
Article
Immunology
Tong Wu, Zhangyi Song, Haiqiu Huang, Tanja Jakos, Hua Jiang, Yueqing Xie, Jianwei Zhu
Summary: A novel immunotoxin GT5 targeting GPC3 was found to effectively inhibit hepatocellular tumor growth, showing promising therapeutic potential.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Review
Medicine, General & Internal
Vittoria Lutje, Katrin Probyn, Jorge Seixas, Hanna Bergman, Gemma Villanueva
Summary: The study evaluated the effectiveness and safety of current drugs for treating second-stage Trypanosoma brucei gambiense trypanosomiasis. Oral treatment with fexinidazole is easier to administer but may lead to higher mortality and relapse compared to conventional treatment.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS
(2021)
Article
Multidisciplinary Sciences
Steven Hyun Seung Lee, Joo Yong Lee, Jun-Sub Choi, Hee Jong Kim, Jin Kim, Seho Cha, Kyoung Jin Lee, Ha-Na Woo, Keerang Park, Heuiran Lee
Summary: This study investigates a gene therapeutic strategy for diabetic retinopathy (DR) using rAAV2-shmTOR-SD, which effectively reduces the progression of DR and has neuroprotective effects.
Article
Chemistry, Medicinal
Saulo Fehelberg Pinto Braga, Rafael Pinto Vieira, Elany Barbosa da Silva, Ludovica Monti, Susann H. Krake, Pablo D. G. Martinez, Luiz Carlos Dias, Conor R. Caffrey, Jair L. Siqueira-Neto, Renata Barbosa de Oliveira, Rafaela Salgado Ferreira
Summary: This study reports potential drugs for diseases caused by two parasites, which showed promising in vitro anti-parasitic activities. One of the drugs is 200 times more potent than the current anti-chagasic drug and has high selectivity against myoblast cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Cecilia Pinna, Tommaso Laurenzi, Fabio Forlani, Luca Palazzolo, Claire Beatrice Nolan, Michael S. S. Christodoulou, Paolo Cortesi, Andrea Pinto, Ivano Eberini, Andrea Kunova, Sabrina Dallavalle
Summary: The European Farm to Fork strategy requires reducing the use of synthetic pesticides, which exposes vulnerable agricultural sectors like European risiculture to devastating diseases and endangers food security. Therefore, novel scaffolds need to be identified for the synthesis of environmentally friendly fungicides.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Peter Riber Johnsen, Cecilia Pinna, Luce Mattio, Mathilde Bech Strube, Mattia Di Nunzio, Stefania Iametti, Sabrina Dallavalle, Andrea Pinto, Hanne Frokiaer
Summary: This study compares the effects of seven different structural types of stilbenoids on the modulation of cytokine production and antioxidant response. Monomeric compounds showed dose-dependent inhibition of cytokine production induced by E. coli, with resveratrol and piceatannol also inhibiting IL-10 production. All monomers, except trimethoxy-resveratrol, inhibited cytokine production induced by L. acidophilus. However, the dimer dehydro-delta-viniferin remarkably enhanced IL-12 production induced by L. acidophilus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Andrea Citarella, Davide Moi, Martina Pedrini, Helena Perez-Pena, Stefano Pieraccini, Claudio Stagno, Nicola Micale, Tanja Schirmeister, Giulia Sibille, Giorgio Gribaudo, Alessandra Silvani, Daniele Passarella, Clelia Giannini
Summary: SARS-CoV-2 M-pro is a significant enzyme in the replication and infectivity of SARS-CoV-2. We synthesized and evaluated MPD112, a novel inhibitor of SARS-CoV-2 M-pro, which displayed inhibition activity at a low micromolar level in vitro. The compound showed selectivity for M-pro and demonstrated good tolerability and biological activity in human cells.
Article
Chemistry, Medicinal
Andrea Galbiati, Stefania Bova, Raffaella Pacchiana, Chiara Borsari, Marco Persico, Aureliano Zana, Stefano Bruno, Massimo Donadelli, Caterina Fattorusso, Paola Conti
Summary: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays a crucial role in cancer cell metabolism and is considered a potential target for anticancer drugs. Compound 11, a spirocyclic derivative, was identified as a covalent inhibitor of human GAPDH (hGAPDH) with higher reactivity than other known inhibitors. Computational studies confirmed the importance of conformational rigidification for stabilizing the interaction between the inhibitor and the binding site. Compound 11 selectively reacted with the activated cysteine of hGAPDH and inhibited cancer cell growth. These findings suggest that compound 11 has potential for the development of anticancer agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Roberta Ettari
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Giulia Culletta, Marco Tutone, Roberta Ettari, Ugo Perricone, Carla Di Chio, Anna Maria Almerico, Maria Zappala
Summary: Inhibition of immunoproteasome is a promising strategy for treating hematological malignancies, autoimmune diseases, and inflammatory diseases. Designing non-covalent inhibitors could overcome the toxicity issues of known covalent inhibitors. In this study, 34 compounds were evaluated, and 7 compounds showed inhibitory activity against immunoproteasome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Andrea Galbiati, Aureliano Zana, Chiara Borsari, Marco Persico, Stefania Bova, Oleh Tkachuk, Alexandra Ioana Corfu, Lucia Tamborini, Nicoletta Basilico, Caterina Fattorusso, Stefano Bruno, Silvia Parapini, Paola Conti
Summary: This study investigated the significance of chirality for the natural compound 3-Br-acivicin (3-BA) and its derivatives. The (5S, aS) isomers displayed significant antiplasmodial activity, suggesting their uptake might be mediated by the L-amino acid transport system. Stereochemistry only affected target binding for two subclasses, but led to significant differences in antimalarial activity for all subclasses, indicating that stereoselective uptake might be responsible for the enhanced activity of (5S, aS) isomers.
Article
Pharmacology & Pharmacy
Min Zhou, Joelle C. Boulos, Ejlal A. Omer, Hadi Amiri Rudbari, Tanja Schirmeister, Nicola Micale, Thomas Efferth
Summary: The study selected two palladium (II) complexes with double chlorine or double iodine substitution, which showed the best cytotoxicity against drug-sensitive leukemia cells. Surprisingly, these complexes induced a novel mode of cell death called parthanatos. This study suggests that these complexes may be potential drug candidates to overcome tumor resistance to apoptosis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Chemistry, Organic
Andrea Citarella, Davide Moi, Martina Pedrini, Helena Perez-Pena, Stefano Pieraccini, Alessandro Dimasi, Claudio Stagno, Nicola Micale, Tanja Schirmeister, Giulia Sibille, Giorgio Gribaudo, Alessandra Silvani, Clelia Giannini, Daniele Passarella
Summary: COVID-19 is one of the most devastating global pandemics in history caused by a new human coronavirus (SARS-CoV-2) that spreads among humans and animals. Efforts have been made to develop therapeutic agents to treat COVID-19, and the cysteine protease SARS-CoV-2 M-pro is considered a promising target. In this study, cinnamic ester was used to inhibit M-pro and showed potential antiviral activity against human coronaviruses.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Sara Vicinanza, Francesca Annunziata, Desiree Pecora, Andrea Pinto, Lucia Tamborini
Summary: A facile and convenient lipase-catalyzed flow approach has been developed for synthesizing tyrosol and hydroxytyrosol methyl carbonates in neat dimethylcarbonate, with quantitative yield and high catalyst productivity. The biocatalytic approach can also be used for preparing value-added symmetrical tyrosol and hydroxytyrosol carbonates.
Article
Chemistry, Physical
Agostina Colacicco, Giorgia Catinella, Cecilia Pinna, Alessandro Pellis, Stefano Farris, Lucia Tamborini, Sabrina Dallavalle, Francesco Molinari, Martina Letizia Contente, Andrea Pinto
Summary: An efficient one-pot, 2-step flow bioprocess has been developed for obtaining the aglycones of hesperidin (HES) and rutin (RT). The strategy involves co-immobilizing commercially available α-rhamnosidase and extremophilic β-glycosidase on glyoxyl-agarose beads to create a high-performing multi-active biocatalyst. By optimizing the reaction conditions and implementing a flow switch, the process achieves high productivity, cost-efficiency, and sustainability.
CATALYSIS SCIENCE & TECHNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Fabiola De Luca, Alessandro Allegra, Carla Di Chio, Santo Previti, Maria Zappala, Roberta Ettari
Summary: Multiple myeloma is an incurable hematologic cancer characterized by immunological alterations in myeloid cells and lymphocytes. The current first-line therapy involves chemotherapy, but there is a high relapse rate and refractory MM cases. New monoclonal antibodies (Mab) including daratumumab, isatuximab, and elotuzumab, along with bispecific antibodies and CAR T cell therapy, have shown promise in immunotherapy for MM. CD38 (daratumumab and isatuximab), SLAM7 (elotuzumab) and BCMA (belantamab mafodotin) are the main antibody targets for MM treatment. Although MM is still incurable, combining the available drugs offers hope for improving outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
