Article
Biochemistry & Molecular Biology
Wagner A. S. Judice, Leticia Silva Ferraz, Rayssa de Mello Lopes, Luan dos Santos Vianna, Fabio da Silva Siqueira, Juliana F. Di Iorio, Laura de Azevedo Maffeis Dalzoto, Mariana Nascimento Romero Trujilho, Taiz dos Reis Santos, Mauricio F. M. Machado, Tiago Rodrigues
Summary: Leishmaniasis and trypanosomiasis are endemic neglected diseases in South America and Africa, posing a significant public health problem. Current therapeutic options have limitations, leading to the search for new targets and treatments. Cysteine proteases are being investigated as promising targets for drug discovery against protozoal neglected diseases.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Leonardo L. G. Ferreira, Josue de Moraes, Adriano D. Andricopulo
Summary: Neglected tropical diseases, such as leishmaniasis and schistosomiasis, continue to be a public health challenge in developing countries. However, advancements in drug discovery using modern strategies have shown promise in addressing these diseases by combining medicinal chemistry and parasite biology.
DRUG DISCOVERY TODAY
(2022)
Review
Nutrition & Dietetics
Wilson Savino, Jonathan Duraes, Carolina Maldonado-Galdeano, Gabriela Perdigon, Daniella Areas Mendes-da-Cruz, Patricia Cuervo
Summary: Undernutrition remains a major issue in global health, especially affecting children under the age of five. Undernutrition compromises the immune system and increases susceptibility to infections. The thymus, as a crucial immune organ, is also affected by undernutrition and infection. Molecular interactions, including hormonal imbalance, play a role in undernutrition-induced thymic atrophy. Recent research has shown potential benefits of probiotic bacteria in improving thymic changes caused by undernutrition.
FRONTIERS IN NUTRITION
(2022)
Review
Immunology
Debora B. Scariot, Austeja Staneviciute, Jennifer Zhu, Xiaomo Li, Evan A. Scott, David M. Engman
Summary: Nanotechnology has been playing an important role in improving drug efficacy and reducing toxicity and side effects. However, the clinical effectiveness of nanomedicines in the treatment of leishmaniasis and Chagas disease is still limited to preliminary animal studies.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Ana Isabel Olias-Molero, Concepcion de la Fuente, Montserrat Cuquerella, Juan J. Torrado, Jose M. Alunda
Summary: Leishmaniasis, caused by Leishmania species, affects humans and animals with no available vaccine and relies mainly on chemotherapy. The currently used drugs are old, toxic, and expensive, with limited efficacy, facing challenges of growing resistance and therapeutic failure. The drug pipeline deconstruction impacts the high failure rate of potential drugs in the fight against this parasitic disease.
Review
Biochemistry & Molecular Biology
Carlos Garcia-Estrada, Yolanda Perez-Pertejo, Barbara Dominguez-Asenjo, Vanderlan Nogueira Holanda, Sankaranarayanan Murugesan, Maria Martinez-Valladares, Rafael Balana-Fouce, Rosa M. Reguera
Summary: Due to the lack of specific vaccines, neglected tropical diseases caused by trypanosomatids, such as sleeping sickness, Chagas disease and leishmaniasis, rely solely on pharmacological treatments. The current drugs have drawbacks including adverse effects, parenteral administration, chemical instability, and high costs. However, the discovery of new drugs for these diseases is rare due to the lack of interest from big pharmaceutical companies. Nitroheterocyclic compounds, such as benznidazole and nifurtimox, have provided potent effects against Chagas disease, and fexinidazole has been developed as a new drug against African trypanosomiasis. Despite being initially discarded due to their mutagenic potential, nitroheterocycles now show promise as a source of inspiration for developing oral drugs to replace existing ones.
Article
Biochemistry & Molecular Biology
Michael J. da Silva, Andrey P. Jacomini, Davana S. Goncalves, Karlos Eduardo Pianoski, Julia Poletto, Danielle Lazarin-Bidoia, Helito Volpato, Celso Nakamura, Fernanda A. Rosa
Summary: A novel tetrasubstituted pyrazole derivative was discovered to exhibit potent and selective inhibition against both L. amazonensis and T. cruzi, offering a new approach for the treatment of Chagas disease and Leishmaniasis.
BIOORGANIC CHEMISTRY
(2021)
Article
Microbiology
Marvin J. Nunez, Morena L. Martinez, Atteneri Lopez-Arencibia, Carlos J. Bethencourt-Estrella, Desiree San Nicolas-Hernandez, Ignacio A. Jimenez, Jacob Lorenzo-Morales, Jose E. Pinero, Isabel L. Bazzocchi
Summary: The study discovered that two celastrol-based compounds found in the root bark of Maytenus chiapensis showed potent inhibitory effects on Leishmania amazonensis and Trypanosoma cruzi, with higher potency than reference drugs. These compounds also demonstrated excellent selectivity on murine macrophages, inducing apoptotic cell death in L. amazonensis triggered by the mitochondria. The findings highlight the potential of celastrols as lead compounds for the development of novel antikinetoplastid drugs.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Review
Pharmacology & Pharmacy
Juliana Correa-Barbosa, Daniele Ferreira Sodre, Pedro Henrique Costa Nascimento, Maria Fani Dolabela
Summary: This study evaluates the potential of plants from the genus Zanthoxylum for treating neglected diseases. The active substances in several species of this genus show promising effects against malaria, leishmaniasis, Chagas disease, and sleeping sickness.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Taisuke Tawaraishi, Atsuko Ochida, Yuichiro Akao, Sachiko Itono, Masahiro Kamaura, Thamina Akther, Mitsuyuki Shimada, Stacie Canan, Sanjoy Chowdhury, Yafeng Cao, Kevin Condroski, Ola Engkvist, Amanda Francisco, Sunil Ghosh, Rina Kaki, John M. Kelly, Chiaki Kimura, Thierry Kogej, Kazuya Nagaoka, Akira Naito, Garry Pairaudeau, Constantin Radu, Ieuan Roberts, David Shum, Nao-aki Watanabe, Huanxu Xie, Shuji Yonezawa, Osamu Yoshida, Ryu Yoshida, Charles Mowbray, Benjamin Perry
Summary: Probing multiple proprietary pharmaceutical libraries in parallel through virtual screening led to the rapid expansion of structure-activity relationship (SAR) around hit compounds with moderate efficacy against Trypanosoma cruzi. The SAR was further developed through a potency-improving scaffold hop and design guided by phenotypic virtual screening, resulting in the identification of two promising hit compounds 54 and 85. Compound 85 showed a significant reduction in parasitemia in an in vivo model, confirming its potential as an anti-trypanosome treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
J. Brindha, M. M. Balamurali, Kaushik Chanda
Summary: Neglected tropical diseases (NTDs) encompass twenty infectious diseases caused by bacteria, viruses, and parasites. Researchers are focusing on developing alternative and novel therapeutics targeting specific biochemical pathways of the causative parasites for diseases like Chagas disease and leishmaniasis. The use of nano-based formulations for therapeutics is also being discussed.
FRONTIERS IN CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Desiree San Nicolas-Hernandez, Carlos J. Bethencourt-Estrella, Atteneri Lopez-Arencibia, Eduardo Hernandez-Alvarez, Ines Sifaoui, Isabel L. Bazzocchi, Jacob Lorenzo-Morales, Ignacio A. Jimenez, Jose E. Pinero
Summary: This study reports the leishmanicidal and trypanocidal activities of twenty-four known silyl-ether derivatives of withaferin A. Among them, derivative 10 exhibited higher activity against Leishmania and Trypanosoma parasites with lower cytotoxicity. These derivatives appear to induce apoptosis-like and autophagy events leading to programmed cell death.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Chemistry, Medicinal
Alisha Ansari, Anuradha Seth, Mukul Dutta, Tooba Qamar, Sarita Katiyar, Arvind K. Jaiswal, Ankita Rani, Swetapadma Majhi, Mukesh Kumar, Rabi S. Bhatta, Rajdeep Guha, Kalyan Mitra, Koneni Sashidhara, Susanta Kar
Summary: In this study, a series of quinazolinone-based acetamide derivatives were synthesized and evaluated for their anti-leishmanial activity. Compounds F12, F27, and F30 exhibited remarkable activity against L. donovani in vitro. Oral administration of F12 and F27 significantly reduced parasite burden in infected mice and hamsters. Mechanistic studies revealed the inhibition of the PI3K/Akt/CREB axis by F27, resulting in a shift from IL-10 to IL-12 release in macrophages. In silico studies suggested that F27 inhibits Leishmania prolyl-tRNA synthetase, leading to programmed cell death of the parasite.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Valter Viana Andrade-Neto, Juliana da Silva Pacheco, Job Domingos Inacio, Elmo Eduardo Almeida-Amaral, Eduardo Caio Torres-Santos, Edezio Ferreira Cunha-Junior
Summary: Translation studies involving drug reuse and combination therapies can lead to higher success rates in drug development, as evidenced by the promising results of spironolactone in treating leishmaniasis. Further research is needed to explore the potential benefits of combining spironolactone with meglumine antimoniate for improved parasite load control.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Guilherme S. Ramos, Virginia M. R. Vallejos, Marina S. Ladeira, Priscila G. Reis, Daniel M. Souza, Yuri A. Machado, Luiz O. Ladeira, Mauricio B. Pinheiro, Maria N. Melo, Ricardo T. Fujiwara, Frederic Frezard
Summary: The study found that fullerol has potential anti-leishmanial activity, especially when combined with liposomes, showing significant reduction in parasite load. This innovative approach provides a new potential method for treating VL.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
