Article
Immunology
Amrita Chakrabarti, Chintam Narayana, Nishant Joshi, Swati Garg, Lalit C. Garg, Anand Ranganathan, Ram Sagar, Soumya Pati, Shailja Singh
Summary: This study chemically synthesized a library of glycoside derivatives and evaluated their inhibitory efficacy against Leishmania donovani. The results showed that Gly2 had the highest inhibitory activity against promastigotes and strong binding affinity towards Gp63. In addition to its lethal effects on infectivity and multiplication, Gly2 also enhanced complement-mediated lysis and showed effectiveness against PKDL strain.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Chemistry, Analytical
Marta Lopes Lima, Maiara Amaral, Samanta Etel Treiger Borborema, Andre Gustavo Tempone
Summary: This study investigates the antileishmanial potential and mechanism of action of the antidepressant escitalopram. The results show that escitalopram selectively kills the parasite by disrupting mitochondria and interfering with the cell cycle.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2022)
Article
Chemistry, Medicinal
Selwan M. El-Sayed, Samar A. Ahmed, Kanika Gulia, Justin R. Lenhard, Ahmed H. E. Hassan, Abdelbasset A. Farahat
Summary: Researchers designed, synthesized, and evaluated new amidine derivatives as antibacterial agents. Compound 13d showed the most potent activity against antibiotic-resistant and susceptible Gram-positive and Gram-negative bacterial strains. The compound was found to be an effective bactericidal agent, and further studies are needed to explore its mode of action and potential as a future antibacterial agent.
Review
Biochemistry & Molecular Biology
Philippe M. Loiseau, Kaluvu Balaraman, Gillian Barratt, Sebastien Pomel, Remy Durand, Frederic Frezard, Bruno Figadere
Summary: This review documents the development of the 2-substituted quinoline series as a potential treatment for leishmaniasis. The series has shown promising antileishmanial activity with low toxicity, and attempts have been made to establish structure-activity relationships and determine the mechanism of action. The molecules in this series appear to act on multiple targets, including the immune system, which may explain the lack of drug resistance observed after in vitro drug pressure. Nanotechnology strategies and mechanistic targeting approaches may enhance the activity of these drugs.
Article
Biochemistry & Molecular Biology
Hans Koss, Barry Honig, Lawrence Shapiro, Arthur G. Palmer
Summary: NMR spectroscopy was used to elucidate the roles of Trp2 and Trp4 in Cadherin-11 dimerization, revealing that the dimerization mechanism of type II cadherins involves coupled folding and strand swapping.
Article
Chemistry, Multidisciplinary
Natalia C. S. Costa, Luana Ribeiro dos Anjos, Joao Victor Marcelino de Souza, Maria Carolina Oliveira de Arruda Brasil, Vitor Partite Moreira, Marcia A. S. Graminha, Gert Lubec, Eduardo Rene P. Gonzalez, Eduardo Maffud Cilli
Summary: Leishmaniasis is a group of diseases caused by protozoa from the Leishmania genus. It poses a significant public health issue, especially with the increasing number of at-risk patients. The currently available treatment options are limited and potentially toxic, necessitating the pursuit of new therapeutic alternatives.
Letter
Multidisciplinary Sciences
Mitchell A. A. Moseng, Chih-Chia Su, Philip A. A. Klenotic, Eric Delpire, Edward W. W. Yu
Summary: Moseng et al. recently reported four cryo-electron microscopy structures of the human Na-K-2Cl cotransporter-1 (hNKCC1), providing high-resolution structural information for both the apo-hNKCC1 structure and its conformational states induced by diuretic drugs. The authors proposed a scissor-like inhibition mechanism based on the structural information, involving coupled movement between the cytosolic and transmembrane domains of hNKCC1. This study has important implications for understanding the inhibition mechanism and the concept of long-distance coupling involving both cytoplasmic and transmembrane domains.
Article
Cell Biology
Wenjian Yao, Xiangbo Jia, Lei Xu, Saisai Li, Li Wei
Summary: The study found that miR-2053 was downregulated in esophageal cancer cells, and its overexpression inhibited cell proliferation, migration, and invasion while promoting apoptosis, potentially through upregulating KIF3C expression and activating the PI3K/AKT signaling pathway in esophageal cancer development.
Article
Chemistry, Medicinal
Ahmed Sabt, Wagdy M. Eldehna, Tamer M. Ibrahim, Adnan A. Bekhit, Rasha Z. Batran
Summary: In this study, new quinoline-isatin hybrids were synthesized and tested for their antileishmanial activity. All compounds showed promising in vitro activity against Leishmania major strain and were found to have higher activity than the reference drug miltefosine. Compounds 4e, 4b, and 4f showed the highest antileishmanial activity against both promastigote and amastigote forms.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Yingru Zhang, Yiyang Zhao, Jingwen Liu, Chunpu Li, Ying Feng, Shasha Jiang, Xiaoting Sun, Xueqing Hu, Yan Wang
Summary: Tanshinone IIA has been proven to effectively prevent tumor growth and increase survival time in colorectal cancer. It alters cell morphology, induces apoptosis in cancer cells, and regulates protein expression through the p38MAPK signaling pathway.
ANALYTICAL CELLULAR PATHOLOGY
(2022)
Article
Chemistry, Medicinal
Alexander F. Kiefer, Spyridon Bousis, Mostafa M. Hamed, Eleonora Diamanti, Joerg Haupenthal, Anna K. H. Hirsch
Summary: Report on a potent class of substituted ureidothiophenes targeting an unexplored target, energy-coupling factor (ECF) transporters, which is not addressed by any antibiotic in the market. These compounds effectively inhibit the membrane-bound protein mediated uptake of folate and have potent antimicrobial activities against a panel of clinically relevant Gram-positive pathogens.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Alexander F. Kiefer, Spyridon Bousis, Mostafa M. Hamed, Eleonora Diamanti, Joerg Haupenthal, Anna K. H. Hirsch
Summary: This study reports on a potent class of substituted ureidothiophenes that target energy-coupling factor (ECF) transporters, a previously unexplored target in the antibiotic market. These compounds effectively inhibit the uptake of folate, a crucial process for vitamin transport, leading to cell death. Furthermore, the optimized compounds exhibit strong antimicrobial activities against clinically relevant Gram-positive pathogens without significant cytotoxic effects.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Alexandros Marios Sofias, Geir Bjorkoy, Jordi Ochando, Linda Sonstevold, Maria Hegvik, Catharina de Lange Davies, Olav Haraldseth, Twan Lammers, Willem J. M. Mulder, Sjoerd Hak
Summary: Active-targeting nanomedicine formulations exhibit complex in vivo behavior, with recent studies showing extensive uptake by circulating phagocytes targeting inflamed lesions. Mechanistically, the targeting of cRGD-NPs towards inflamed lesions is similar to NP accumulation in cancerous lesions. Circulating phagocytes engage cRGD-NPs and are homed to the inflamed endothelium, contributing to the extensive presence of cRGD-NP-positive phagocytes in angiogenic vessels. This study highlights the importance of detailed investigations into the in vivo behavior of nanoparticles for their potential as advanced therapeutic agents.
Article
Infectious Diseases
Douglas O. Escrivani, Rebecca L. Charlton, Marjolly B. Caruso, Gabriela A. Burle-Caldas, Maria Paula G. Borsodi, Russolina B. Zingali, Marcos Palmeira-Mello, Jessica B. de Jesus, Alessandra M. T. Souza, Barbara Abrahim-Vieira, Stefanie Freitag-Pohl, Ehmke Pohl, Paul W. Denny, Bartira Rossi-Bergmann, Patrick G. Steel
Summary: This study identified a novel broad-spectrum antileishmanial drug lead by targeting cytosolic tryparedoxin peroxidase with a chemical probe, leading to parasite death without host toxicity. The findings highlight the importance of cTXNPx as a potential drug target for antileishmanial chalcones, providing a promising avenue for future drug discovery programs.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Multidisciplinary Sciences
Yuxiang Zhou, David Hou, Cristina Cusco Marigo, Joaquin Bonelli, Pau Rocas, Fangzhou Cheng, Xiaoqiu Yang, Josep Rocas, Naomi M. Hamberg, Jingyan Han
Summary: Aortic endothelial cell dysfunction is a trigger of atherosclerosis. This study investigates the efficacy of nanocapsules in delivering fluorescent dye to the vascular system, showing its potential as a therapeutic solution for cardiovascular disease.