Article
Biochemistry & Molecular Biology
Trong-Nhat Phan, Kyuho Paul Park, Diego Benitez, Marcelo A. Comini, David Shum, Joo Hwan No
Summary: Leishmaniasis is an infectious disease caused by the protozoa Leishmania, with high infection and death rates in developing countries. New drugs with improved pharmacological properties are urgently needed. Trypanothione synthetase (TryS) is a promising target for drug development against leishmaniasis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Immunology
Job D. F. Inacio, Myslene S. Fonseca, Gabriel Limaverde-Sousa, Ana M. Tomas, Helena Castro, Elmo E. Almeida-Amaral
Summary: EGCG kills Leishmania infantum promastigotes by disrupting their intracellular redox balance through mechanisms including mitochondrial depolarization, decreased intracellular ATP levels, increased intracellular H2O2 levels, and potentially acting as a competitive inhibitor of the enzyme trypanothione reductase.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Chemistry, Medicinal
Hector de Lucio, Alejandro Revuelto, Alejandra A. Carriles, Sonia de Castro, Sonia Garcia-Gonzalez, Juan Carlos Garcia-Soriano, Mercedes Alcon-Calderon, Pedro A. Sanchez-Murcia, Juan A. Hermoso, Federico Gago, Maria-Jose Camarasa, Antonio Jimenez-Ruiz, Sonsoles Velazquez
Summary: N-methylation of triazole-phenyl-thiazole dimerization disruptors led to potent inhibitors against Leishmania infantum trypanothione disulfide reductase (LiTryR), targeting different binding sites. Subtle structural changes modified their mechanism of action, resulting in improved potency and selectivity against the parasite.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Marwa S. Osman, Talal A. Awad, Shaza W. Shantier, Elrashied A. Garelnabi, Wadah Osman, Ramzi A. Mothana, Fahd A. Nasr, Rashid I. Elhag
Summary: Chalcone analogues were synthesized and evaluated for their potential as antileishmanial agents. Chalcone 4 exhibited the highest inhibitory effect with good pharmacokinetic and toxicological properties. Molecular dynamics simulation revealed the activity and stability of Chalcone 4 as a trypanothione reductase (TR) inhibitor.
ARABIAN JOURNAL OF CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Julieta Coro-Bermello, Ernesto R. Lopez-Rodriguez, Javier E. Alfonso-Ramos, Dayana Alonso, Gerardo M. Ojeda-Carralero, Gustavo A. Prado, Elena Moreno-Castillo
Summary: This study identified new thiadiazine-based compounds as potential candidates for selectively inhibiting the parasitic enzyme responsible for Chagas disease. Molecular docking analysis revealed diverse binding modes for hybrid ligands, with an assessment of potential cytotoxicity towards human cells. The research provides insights into developing new treatments for Chagas disease.
SN APPLIED SCIENCES
(2021)
Article
Infectious Diseases
Kaio Maciel De Santiago-Silva, Bruna Taciane da Silva Bortoleti, Laudicea do Nascimento Oliveira, Fernanda Lima de Azevedo Maia, Joyce Cristina Castro, Ivete Conchon Costa, Danielle Bidoia Lazarin, James L. Wardell, Solange M. S. Wardell, Magaly Girao Albuquerque, Camilo Henrique da Silva Lima, Wander Rogerio Pavanelli, Marcelle de Lima Ferreira Bispo, Raoni Schroeder B. Goncalves
Summary: Leishmaniasis is a neglected tropical disease with limited therapeutic options. In this study, new compounds were synthesized and evaluated for their biological activity against different forms of Leishmania parasites. Compound 4f showed the most promising results, exhibiting potent inhibitory effects on promastigotes and low toxicity to cells.
Article
Biochemistry & Molecular Biology
Sarra Maamri, Khedidja Benarous, Mohamed Yousfi
Summary: The study identified the potential of 3-Methoxycarpachromene and Masticadienonic acid in combating Leishmania parasites, with promising results from molecular docking analysis, suggesting their significance in drug discovery in treating leishmaniasis.
Article
Biochemistry & Molecular Biology
Shoko Matsuoka, Karin Sato, Riyo Maruki-Imamura, Yoshiteru Noutoshi, Takayoshi Okabe, Hirotatsu Kojima, Taishi Umezawa
Summary: ABA is a key phytohormone that regulates plant stress responses and development, and SnRK2 is a key regulator of ABA signaling. Through high-throughput screening, ten potential inhibitors of SnRK2 activity were identified, with three showing specific inhibition of SnRK2 kinase activity. Seven of the compounds inhibited ABA responsive gene expression in Arabidopsis cells. This study suggests that INH1 could be a lead compound for studying ABA responses in different plant species.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
A. Zabala-Penafiel, G. Dias-Lopes, F. Souza-Silva, L. F. C. Miranda, F. Conceicao-Silva, C. R. Alves
Summary: Leishmania parasites have a defense mechanism called the trypanothione system, which plays a central role in processing pentavalent antimony and is related to resistance. The study assessed the effect of trivalent and pentavalent antimony on Trypanothione Reductase activity in two clinical isolates of Leishmania (Viannia) braziliensis. The results showed differences in susceptibility profiles and trypanothione reductase activity between the isolates.
Article
Immunology
Xiaojing Wen, Li Zhang, Shan Zhao, Qiang Liu, Wenyi Guan, Jiajing Wu, Qiwei Zhang, Hongling Wen, Weijin Huang
Summary: The study found that cardamomin has good anti-human adenovirus 5 (HAdV5) activity both in vitro and in vivo, and can protect tissues from virus-induced damage. This research established a method for high-throughput screening of anti-HAdV5 drugs and demonstrated cardamomin as a potential new treatment for patients infected with adenoviruses.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Parasitology
Minelly A. da Silva, Harold H. Fokoue, Saara N. Fialho, Ana Paula de A. dos Santos, Norton R. D. L. P. Rossi, Aurileya de J. Gouveia, Amalia S. Ferreira, Guilherme M. Passarini, Ana F. G. Garay, Jorge J. Alfonso, Andreimar M. Soares, Fernando B. Zanchi, Massuo J. Kato, Carolina B. G. Teles, Christian C. Kuehn
Summary: Leishmaniasis is considered a neglected disease, leading to a lack of financial motivation for research efforts in finding biologically active substances. This study identified compounds with promising leishmanicidal activity, such as piplartine, and investigated their possible mechanisms of action.
PARASITOLOGY RESEARCH
(2021)
Article
Chemistry, Medicinal
Alejandro Revuelto, Isabel Lopez-Martin, Hector de Lucio, Juan Carlos Garcia-Soriano, Nicola Zanda, Sonia de Castro, Federico Gago, Antonio Jimenez-Ruiz, Sonsoles Velazquez, Maria-Jose Camarasa
Summary: By disrupting protein-protein interactions at the dimer interface of Leishmania infantum TryR, researchers have developed a novel series of small-molecule-peptide conjugates that show good inhibitory effects on both enzyme activity and dimerization.
Article
Chemistry, Medicinal
Omar Casanova-Alvarez, Aliuska Morales-Helguera, Miguel Angel Cabrera-Perez, Reinaldo Molina-Ruiz, Christophe Molina
Summary: In this study, an automated workflow was developed for predicting antileishmanial activity, utilizing a large, diverse, and highly imbalanced dataset of compounds. The workflow implemented a novel strategy based on balanced training sets and a consensus model using decision trees, resulting in improved predictive accuracy for the test and external sets when compared to other base models like Gaussian-Naive-Bayes and Support-Vector-Machine. The consensus model was found to be effective in prioritizing active compounds with high prediction sensitivity, demonstrating the importance of this approach in QSAR problems.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biochemistry & Molecular Biology
Valentina Noemi Madia, Davide Ialongo, Elisa Patacchini, Cecile Exertier, Lorenzo Antonelli, Gianni Colotti, Antonella Messore, Valeria Tudino, Francesco Saccoliti, Luigi Scipione, Andrea Ilari, Roberta Costi, Roberto Di Santo
Summary: This research focused on the design and synthesis of new compounds structurally related to compound 1, and evaluated their inhibition activity on trypanothione reductase (TR) from Leishmania infantum. The results showed that compounds 2a and 2b were the most potent inhibitors, suggesting the potential of an additional aromatic ring for enzymatic inhibition. Further studies are needed to optimize the activity of these compounds through structure-activity relationships.
Review
Biochemistry & Molecular Biology
Rosette N. Tamaddondoust, Alicia Wong, Megha Chandrashekhar, Edouard I. Azzam, Tommy Alain, Yi Wang
Summary: The biological impact of ionizing radiation on humans depends on both the physical properties and absorbed dose of radiation, as well as the unique susceptibility of the exposed individual. DNA is a critical target of radiation, and the damage response is important for maintaining genomic integrity. Unrepaired DNA lesions can lead to mutations and adverse health effects. Cellular sensitivity to radiation is correlated with the ability to repair DNA lesions, and recent studies have used whole-genome analysis to identify genes that impact individual sensitivity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Public, Environmental & Occupational Health
Michele Spinicci, Lorenzo Zammarchi, Marina Gramiccia, Trentina Di Muccio, Dario Bartolozzi, Paola Corsi, Michele Trotta, Alessandro Bartoloni
JOURNAL OF TRAVEL MEDICINE
(2021)
Review
Pharmacology & Pharmacy
Luciana Mosca, Andrea Ilari, Francesco Fazi, Yehuda G. Assaraf, Gianni Colotti
Summary: Taxanes have been widely used as microtubule-targeting antitumor agents since 1984, showing impacts on key molecular mechanisms and cellular processes in cancer treatment. Research into the diverse effects and molecular mechanisms of taxanes may lead to more rational and efficacious applications, as well as novel strategies to overcome drug resistance in cancer therapy.
DRUG RESISTANCE UPDATES
(2021)
Article
Biochemistry & Molecular Biology
Theo Battista, Gianmarco Pascarella, David Sasah Staid, Gianni Colotti, Jessica Rosati, Annarita Fiorillo, Alessia Casamassa, Angelo Luigi Vescovi, Barbara Giabbai, Marta Stefania Semrau, Sergio Fanelli, Paola Storici, Ferdinando Squitieri, Veronica Morea, Andrea Ilari
Summary: The study utilized a drug repositioning strategy to identify six drugs that can directly bind sigma 1R and improve the growth of cells from Huntington disease patients. These drugs have shown efficacy in providing new therapeutic tools against HD, offering hope for future treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Sergio Mallart, Raffaele Ingenito, Elisabetta Bianchi, Alberto Bresciani, Simone Esposito, Mariana Gallo, Paola Magotti, Edith Monteagudo, Laura Orsatti, Daniela Roversi, Alessia Santoprete, Federica Tucci, Maria Veneziano, Regine Bartsch, Claudius Boehm, Denis Brasseur, Patricia Bruneau, Alain Corbier, Jacques Froissant, Laurence Gauzy-Lazo, Vincent Gervat, Frank Marguet, Isabelle Menguy, Claire Minoletti, Marie-Francoise Nicolas, Olivier Pasquier, Bruno Poirier, Alexandre Raux, Laurence Riva, Philip Janiak, Hartmut Strobel, Olivier Duclos, Stephane Illiano
Summary: This study involves the development of long-acting potent single-chain relaxin peptide mimetics by modifying the B-chain of relaxin, introducing specific mutations and trimming the sequence to an optimal size. These modifications resulted in potent, structurally simplified peptide agonists of the relaxin receptor RXFP1, with high subcutaneous bioavailability and extended half-lives, showing in vivo efficacy.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Valerio Chiarini, Annarita Fiorillo, Serena Camerini, Marco Crescenzi, Shin Nakamura, Theo Battista, Leonardo Guidoni, Gianni Colotti, Andrea Ilari
Summary: The study revealed that zinc ion can activate the protein splicing of BIL2, leading to ubiquitination through the formation of a covalent isopeptide bond. Additionally, ubiquitination of T.thRas-GTPase was found to stabilize the protein's active state.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Review
Biochemistry & Molecular Biology
Ilaria Genovese, Marianna Carinci, Lorenzo Modesti, Gianluca Aguiari, Paolo Pinton, Carlotta Giorgi
Summary: Mitochondria play crucial roles in cell survival through various mechanisms, and their dysregulation can lead to cell death. Chemoresistance in cancer is often associated with the cooperation of multiple cellular protection mechanisms, including those related to mitochondria.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Anna Barile, Theo Battista, Annarita Fiorillo, Martino Luigi di Salvo, Francesco Malatesta, Angela Tramonti, Andrea Ilari, Roberto Contestabile
Summary: PLP, the active form of vitamin B6, is crucial in metabolism as an enzyme cofactor. In Escherichia coli, PNPO catalyzes PLP formation and is inhibited by the same molecule through allosteric regulation. Crystallographic studies identified the allosteric site of PLP on PNPO, and mutagenesis of the arginine cage can modulate the enzyme's allosteric properties.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Health Care Sciences & Services
Annarita Fiorillo, Veronica Morea, Gianni Colotti, Andrea Ilari
Summary: Huntington Disease is a lethal neurodegenerative disorder caused by the abnormal expansion of the HTT gene, and current research suggests that degrading mHtt through the ubiquitin-proteasome system plays a more crucial role in delaying disease progression. PROTACs, which can target specific E3 ubiquitin ligases, may be a promising strategy for Huntington Disease therapy.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Chemistry, Medicinal
Theo Battista, Stefano Federico, Simone Brogi, Luca Pozzetti, Tuhina Khan, Stefania Butini, Anna Ramunno, Eleonora Fiorentino, Stefania Orsini, Trentina Di Muccio, Annarita Fiorillo, Cecile Exertier, Daniel Di Risola, Andrea Ilari, Giuseppe Campiani, Gianni Colotti, Sandra Gemma
Summary: Leishmania spp. is a significant public health issue, and developing better therapeutic drugs is urgently needed. This study optimized a novel class of Leishmania inhibitors through various approaches and identified potent and selective compounds that could be used for treating leishmaniasis and related diseases.
ACS INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Annarita Fiorillo, Gianni Colotti, Cecile Exertier, Anastasia Liuzzi, Francesca Seghetti, Alessandra Salerno, Jessica Caciolla, Andrea Ilari
Summary: Trypanothione reductase (TR) plays a key role in the redox homeostasis of trypanosomatid parasites and is essential for their survival in the oxidative environment. We conducted a fragment-based crystal screening and identified 12 new ligands binding to five different sites, including an allosteric pocket named the doorstop pocket, which hampers TR activity. Another site, known as the Z-site, located within the trypanothione cavity, has not yet been explored for inhibition.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Valentina Noemi Madia, Davide Ialongo, Elisa Patacchini, Cecile Exertier, Lorenzo Antonelli, Gianni Colotti, Antonella Messore, Valeria Tudino, Francesco Saccoliti, Luigi Scipione, Andrea Ilari, Roberta Costi, Roberto Di Santo
Summary: This research focused on the design and synthesis of new compounds structurally related to compound 1, and evaluated their inhibition activity on trypanothione reductase (TR) from Leishmania infantum. The results showed that compounds 2a and 2b were the most potent inhibitors, suggesting the potential of an additional aromatic ring for enzymatic inhibition. Further studies are needed to optimize the activity of these compounds through structure-activity relationships.
Review
Biochemistry & Molecular Biology
Roberto Mattioli, Andrea Ilari, Beatrice Colotti, Luciana Mosca, Francesco Fazi, Gianni Colotti
Summary: Anthracyclines are important and effective treatments for cancer, but their use is complicated by severe side effects and toxicity, including cardiotoxicity. The mode of action of anthracyclines is complex, and their high toxicity may be due to multiple mechanisms. The development of resistance to anthracyclines is a major barrier, but recent studies have addressed this issue. This article provides an overview of anthracycline use in cancer therapy, discussing their mechanisms of action, toxicity, and chemoresistance, as well as approaches to improve their effectiveness, reduce toxicity, and overcome resistance.
MOLECULAR ASPECTS OF MEDICINE
(2023)