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
Chemistry, Multidisciplinary
Crhisllane Rafaele dos Santos Vasconcelos, Antonio Mauro Rezende
Summary: Leishmaniasis, a neglected infectious disease, was studied using computational methods to evaluate potential drug targets in the predicted proteomes of Leishmania braziliensis and Leishmania infantum, revealing several untested proteins with potential therapeutic value.
FRONTIERS IN CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Agni F. M. Gavriilidou, Kleitos Sokratous, Hsin-Yung Yen, Luigi De Colibus
Summary: Studying protein-ligand interactions can greatly assist in the design of new therapeutic molecules. Various techniques used in drug discovery, such as isothermal titration calorimetry and nuclear magnetic resonance spectroscopy, rely on protein crystallography and cryo-electron microscopy. Native mass spectrometry is a versatile method for studying proteins and their interactions, providing valuable insights into protein structure and thermodynamics.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Physical
Matthew Bain, Jose L. Godinez Castellanos, Stephen E. Bradforth
Summary: High-repetition-rate lasers have the potential to revolutionize ultrafast spectroscopy by enabling routine analysis for machine learning models in the design of photochemical syntheses. In this study, we combine innovations in line scan cameras and micro-electro-mechanical grating modulators with high-pressure liquid chromatography pumps to develop a transient absorption spectrometer that can characterize photoreactions in minutes. Additionally, we demonstrate the utility of this technique in exploring the effects of conformational modification on excited-state processes.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Sarah Kymberly Santos de Lima, Jessica Adriana Jesus, Cristiano Raminelli, Marcia Dalastra Laurenti, Luiz Felipe Domingues Passero
Summary: The aim of this study was to demonstrate the leishmanicidal activity of 8-hydroxyquinoline (8-HQ) in vitro and in vivo. The results showed that 8-HQ eliminated promastigote and intracellular amastigote forms of all species studied, and it was more selective than miltefosine. Treatment with 8-HQ significantly reduced tissue parasite numbers in infected animals and led to a reduction in inflammatory reaction in the skin. Therefore, 8-HQ is a promising alternative for the treatment of leishmaniasis.
Article
Multidisciplinary Sciences
Priyanka Parijat, Saraswathi Ponnam, Seetharamaiah Attili, Kenneth S. Campbell, Mohammed El-Mezgueldi, Mark Pfuhl, Thomas Kampourakis
Summary: The unmet demand for new heart failure therapeutics is well recognized and targeting the contractile myofilaments has shown potential for the development of new drugs. However, limited clinical use and incomplete understanding of myofilament function have hindered progress in this area. In this study, new high throughput screening platforms were designed and validated to explore the effects of small molecule effectors on the interactions between cardiac troponin C and troponin I subunits. The results suggest that sarcomeric protein-directed screening platforms are suitable for developing compounds that modulate cardiac myofilament function.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Marko Jukic, Rodolphe Auger, Victor Folcher, Matic Proj, Helene Barreteau, Stanislav Gobec, Thierry Touze
Summary: The study identified small molecules that inhibit the activity of BacA, an enzyme involved in the recycling of undecaprenyl pyrophosphate. The compounds showed significant inhibition of the enzyme's activity and also demonstrated antibacterial activity against Escherichia coli strains.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Review
Agriculture, Dairy & Animal Science
Jacob van der Ende, Henk D. F. H. Schallig
Summary: This review examines the different animal models used in drug development for leishmaniasis and highlights the lack of thorough description of experimental procedures, ethical review, and consideration of alternative methods to animal studies. The study proposes a more standardized animal model and emphasizes the importance of reporting and ethical review. Overall, animal experiments for leishmaniasis drug development are poorly designed, lacking essential information and consideration of animal welfare.
Article
Chemistry, Medicinal
Yiwei Zhang, Jiabei Guo, Jiongjia Cheng, Zhenghua Zhang, Fenghua Kang, Xiaoxing Wu, Qian Chu
Summary: Therapeutic peptides have revolutionized treatment for many human diseases. In recent decades, stapled helical peptides have made rapid progress in drug discovery. Compared to unstabilized linear peptides, stapled helical peptides have shown superior binding affinity, selectivity, membrane permeability, and metabolic stability, offering exciting potential for targeting challenging protein-protein interfaces. This Perspective summarizes the recent use of high-throughput screening technologies for identifying potent stapled helical peptides with optimized binding properties, aiming to accelerate the development of stapled helical peptides as the next generation of therapeutic peptides for various human diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Shasha Liu, Pengfei She, Zehao Li, Yimin Li, Linhui Li, Yifan Yang, Linying Zhou, Yong Wu
Summary: High incidences of urinary tract infection caused by aminoglycosides-resistant E. coli pose a severe burden on public health. This study investigates the antimicrobial activity of the antifungal benzoxaborole drug tavaborole, and its synergistic interaction with aminoglycosides against multidrug resistant E. coli. The results suggest that tavaborole can slow the development of resistance to aminoglycosides and reduce invasiveness of E. coli in combination with tobramycin. Further research is needed to understand the mechanism of action. Tavaborole also exhibits low toxicity and enhances the bactericidal activity of aminoglycosides in an experimental mouse model. These findings indicate the potential of tavaborole as a novel adjuvant to combat drug resistant E. coli and highlight the need for the discovery of more benzoxaborole analogues.
Article
Multidisciplinary Sciences
Zhenzhen Wang, Jiangjiexing Wu, Jia-Jia Zheng, Xiaomei Shen, Liang Yan, Hui Wei, Xingfa Gao, Yuliang Zhao
Summary: The study uses density functional theory calculations to investigate the principles behind the SOD-like catalytic activity of nanomaterials, proposing energy level and adsorption energy principles for quantitatively describing the activity. These principles were validated through experiments on metal-organic frameworks and can be easily implemented in computer programs for screening NMs with intrinsic SOD-like activity. A general predicting theory for superoxide-dismutase mimicking nanomaterials is currently lacking.
NATURE COMMUNICATIONS
(2021)
Review
Chemistry, Multidisciplinary
Xabier Rodriguez-Martinez, Enrique Pascual-San-Jose, Mariano Campoy-Quiles
Summary: The discovery of novel high-performing materials in organic solar cells has rapidly increased efficiency, but traditional experimentation methods are unable to evaluate the vast catalog of materials efficiently. High-throughput experimental and computational methods are being utilized to accelerate the discovery of new materials, with machine-learning algorithms playing a key role in retrieving quantitative structure-activity relationships.
ENERGY & ENVIRONMENTAL SCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Zihan Yang, Zhihang Zhou, Tongxu Si, Zhengdong Zhou, Li Zhou, Y. Rebecca Chin, Liang Zhang, Xinyuan Guan, Mengsu Yang
Summary: Cancer metastasis is a major cause of cancer-related death, and it is characterized by excessive extracellular matrix deposition and increased stiffness in solid tumors. The confined migration of tumor cells in these conditions plays a crucial role in metastasis, but inhibitors specifically targeting this type of migration are rare. In this study, a microfluidic chip was designed to screen for drugs that can effectively inhibit confined migration of cancer cells. By applying this chip, three novel inhibitors of confined migration, MA-5, SB-705498, and diphenyleneiodonium chloride, were discovered in multiple cancer types. The mechanisms of action of these inhibitors were found to be targeting mitochondria, actin polymerization, and cell viability, respectively. Overall, a high-throughput microfluidic platform for screening drugs targeting confined migration was established, and three effective inhibitors were identified.
Review
Biotechnology & Applied Microbiology
Hasan Aldewachi, Radhwan N. Al-Zidan, Matthew T. Conner, Mootaz M. Salman
Summary: Neurodegenerative diseases are incurable conditions that cause progressive degeneration or death of nerve cells. Identifying therapeutic targets and new treatments is a major challenge, and high-throughput screening plays a key role in improving drug discovery efficiency.
BIOENGINEERING-BASEL
(2021)
Article
Chemistry, Medicinal
Alexander Neumann, Isaac Attah, Haneen Al-Hroub, Vigneshwaran Namasivayam, Christa E. Mueller
Summary: The human ATP- and UTP-activated P2Y2 receptor plays a role in various pathological conditions. However, the current P2Y2 receptor antagonists have limitations. In this study, researchers utilized virtual screening and molecular docking to discover novel antagonist scaffolds for the P2Y2 receptor. The identified compounds showed similar binding modes with a known potent orthosteric antagonist. This study provides a basis for the development of future drug candidates for the P2Y2 receptor.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemistry & Molecular Biology
Helena Andrade, Alvin K. Thomas, Weilin Lin, Francesco V. Reddavide, Yixin Zhang
Article
Biochemistry & Molecular Biology
Lena Keller, Jair L. Siqueira-Neto, Julia M. Souza, Korina Eribez, Gregory M. LaMonte, Jennifer E. Smith, William H. Gerwick
Article
Infectious Diseases
Jacob M. Wozniak, Tatiana Araujo Silva, Diane Thomas, Jair L. Siqueira-Neto, James H. McKerrow, David J. Gonzalez, Claudia M. Calvet
PLOS NEGLECTED TROPICAL DISEASES
(2020)
Article
Microbiology
Jean A. Bernatchez, Emily Chen, Mitchell Hull, Case W. McNamara, James H. McKerrow, Jair L. Siqueira-Neto
Article
Oncology
Briana C. Prager, Harish N. Vasudevan, Deobrat Dixit, Jean A. Bernatchez, Qiulian Wu, Lisa C. Wallace, Shruti Bhargava, Derrick Lee, Bradley H. King, Andrew R. Morton, Ryan C. Gimple, Melike Pekmezci, Zhe Zhu, Jair L. Siqueira-Neto, Xiuxing Wang, Qi Xie, Clark Chen, Gene H. Barnett, Michael A. Vogelbaum, Stephen C. Mack, Lukas Chavez, Arie Perry, David R. Raleigh, Jeremy N. Rich
Article
Infectious Diseases
Claudia Magalhaes Calvet, Tatiana Araujo Silva, Diane Thomas, Brian Suzuki, Ken Hirata, Jair Lage Siqueira-Neto, James H. McKerrow
PLOS NEGLECTED TROPICAL DISEASES
(2020)
Article
Infectious Diseases
Isabel S. Shiratsubaki, Xin Fang, Rodolpho O. O. Souza, Bernhard O. Palsson, Ariel M. Silber, Jair L. Siqueira-Neto
PLOS NEGLECTED TROPICAL DISEASES
(2020)
Article
Biochemistry & Molecular Biology
Ileana Slavin, Steven Dea, Priyanka Arunkumar, Neha Sodhi, Sandro Montefusco, Jair Siqueira-Neto, Janet Seelke, Mary Anne Lofstrom, Blake Anson, Fabian Zanella, Cassiano Carromeu
Summary: In response to the increasing global health threats, there is an urgent need to develop and deploy safe and effective therapies rapidly. Repurposing already approved therapeutics for new indications may lead to undesirable side effects due to changes in dosage, usage directives, and clinical context. Studies have shown that many compounds have high toxicity on early-stage neural tissues but not on later stages, emphasizing the importance of utilizing human neural cultures at different developmental stages to understand the neurotoxicity profile of potential therapeutics fully.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Microbiology
Adwaita R. Parab, Diane Thomas, Sharon Lostracco-Johnson, Jair L. Siqueira-Neto, James H. McKerrow, Pieter C. Dorrestein, Laura-Isobel McCall
Summary: Cutaneous leishmaniasis, caused by infection with a Leishmania parasite, affects 700,000 to 1.2 million new cases per year worldwide. Studying disease metabolism at the site of infection may lead to new targets for host-targeted drug development.
Article
Infectious Diseases
Danya A. Dean, Gautham Gautham, Jair L. Siqueira-Neto, James H. McKerrow, Pieter C. Dorrestein, Laura-Isobel Mccall
Summary: Chagas disease, caused by Trypanosoma cruzi, affects millions of people worldwide and can induce severe cardiac symptoms during the chronic stage. By analyzing the heart tissue metabolome of mice infected with T. cruzi, researchers identified specific metabolic changes in localized cardiac regions, highlighting the impact of parasite infection on host metabolism. Furthermore, discriminatory small molecules related to infection were identified, providing insight into the development of chronic cardiac symptoms in CD.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Chemistry, Medicinal
Ittipat Meewan, Jacob Kattoula, Julius Y. Kattoula, Danielle Skinner, Pavla Fajtova, Miriam A. Giardini, Brendon Woodworth, James H. McKerrow, Jair Lage de Siqueira-Neto, Anthony J. O'Donoghue, Ruben Abagyan
Summary: Inhibitors containing thiuram disulfide or dithiobis-(thioformate) were found to be potential drugs against SARS-CoV-2. These compounds showed strong inhibitory effects in enzymatic and cell-based assays, suggesting their promise in the treatment of the COVID-19 virus or related variants.
Article
Biochemistry & Molecular Biology
Jose Renato Pattaro-Junior, Ingrid Garcia Araujo, Carolina Borsoi Moraes, Cecilia Gomes Barbosa, Gisele Strieder Philippsen, Lucio Holanda Freitas-Junior, Ana Carolina Guidi, Joao Carlos Palazzo de Mello, Rosane Marina Peralta, Maria Aparecida Fernandez, Robson Ricardo Teixeira, Flavio Augusto Vicente Seixas
Summary: This study aimed to find potential compounds inhibiting SARS-CoV-2 from extracts of Brazilian plants. Experimental validation showed that ethyl acetate fraction and F2, F4 sub-fractions of C. pluviosum extract exhibited good antiviral activity in infected cells. These results may be attributed to the synergistic effect of different hydrolyzable tannins present in the extract.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Nanoscience & Nanotechnology
Monica Josiane Rodrigues-Jesus, Marianna Teixeira de Pinho Favaro, Alexia Adrianne Venceslau-Carvalho, Maria Fernanda de Castro-Amarante, Bianca da Silva Almeida, Mariangela de Oliveira Silva, Robert Andreata-Santos, Cecilia Gomes Barbosa, Samantha Carvalho Maia Brito, Lucio H. Freitas-Junior, Silvia Beatriz Boscardin, Luis Carlos de Souza Ferreira
Summary: This study reports a COVID-19 subunit vaccine based on nano-multilamellar vesicles (NMV) and monophosphoryl lipid A (MPLA) technology. The research shows that the vaccine can improve antibody and T-cell responses without toxic effects. Additionally, the vaccine formulation reduces the number of doses required to achieve enhanced serum virus-neutralizing antibody titers.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2022)
Review
Biotechnology & Applied Microbiology
Jair L. Siqueira-Neto, Kathryn J. Wicht, Kelly Chibale, Jeremy N. Burrows, David A. Fidock, Elizabeth A. Winzeler
Summary: Recent efforts in antimalarial drug discovery aim to develop new drugs that can overcome emerging drug resistance, consider safety and improve dosing convenience. These efforts have led to the discovery of a variety of new molecules with novel modes of action, some of which are currently in late-stage clinical development. Prioritizing new drug candidates is crucial due to limited funding, and these candidates should demonstrate high potency, low resistance, infrequent dosing, low cost, safety and tolerability, and preferably the ability to block Plasmodium transmission. This review provides insights into successful approaches, progress in preclinical and clinical development, and challenges in antimalarial drug discovery.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Article
Multidisciplinary Sciences
Victor Bolsanelli Cioffi, Maria Fernanda de Castro-Amarante, Aleksei Lulla, Robert Andreata-Santos, Mario Costa Cruz, Ana Carolina Ramos Moreno, Mariangela de Oliveira Silva, Bianca de Miranda Peres, Lucio Holanda Gondim de Freitas Junior, Carolina Borsoi Moraes, Edison Luiz Durigon, Nicola Coker Gordon, Marko Hyvoenen, Luis Carlos de Souza Ferreira, Andrea Balan
Summary: This study utilized the RAD display system to present peptides derived from the SARS-CoV-2 Spike protein, leading to the detection of specific antibodies and the generation of inhibitory antibodies against viral infection. The RAD display system shows promise as a platform for peptide-based vaccine antigen design, epitope-specific antibody mapping, and the development of diagnostic and therapeutic antibodies.
SCIENTIFIC REPORTS
(2023)
