Article
Chemistry, Multidisciplinary
Kefurong Deng, Yachao Li, Xiaoyu Liang, Cheng Shen, Zenan Zeng, Xianghui Xu
Summary: This study developed virus-inspired nanodrugs for high-efficiency antibiotic delivery and enhanced antibacterial effects, demonstrating their potential application in antibacterial treatment.
CHINESE CHEMICAL LETTERS
(2022)
Article
Infectious Diseases
Pietro Picconi, Charlotte K. Hind, J. Mark Sutton, Khondaker Miraz Rahman
Summary: Finding new antibiotic classes against multidrug-resistant bacteria is urgently needed. Pyrrolobenzodiazepines (PBDs) with a C8-linked aliphatic-heterocycle have recently been identified as a new broad-spectrum antibiotic class with activity against Gram-negative bacteria. By replacing the active imine moiety of lead PBD compounds with amide, non-DNA binding and noncytotoxic dilactam analogues were obtained to improve the safety potential of this class.
Article
Infectious Diseases
Chunhong Liang, Xueyan Zhang, Lijuan Zhou, Guangyi Meng, Liqiu Zhong, Pingzhi Peng
Summary: A study conducted in a tertiary-care teaching hospital in southern China from 2012 to 2019 revealed significant correlations between antibiotic consumption and carbapenem resistance rates in Gram-negative bacteria. The findings suggest that implementing proper management strategies and reducing the unreasonable use of antibacterial drugs may help in reducing the spread of carbapenem-resistant Gram-negative bacteria.
BMC INFECTIOUS DISEASES
(2021)
Article
Biochemical Research Methods
Martina Traykovska, Robert Penchovsky
Summary: In recent decades, antibiotic drug resistance has become a significant challenge in modern medicine due to the emergence of bacteria strains resistant to known antibiotics. Riboswitches have emerged as novel targets for antibacterial drug discovery. This study describes the design and applications of antisense oligonucleotides as antibacterial agents targeting riboswitches, demonstrating their suitability for drug development.
ACS SYNTHETIC BIOLOGY
(2022)
Review
Infectious Diseases
Dayse Pereira Dias Silva, Macley Silva Cardoso, Alexandre Jose Macedo
Summary: Bacterial resistance is a major driving force in the worldwide search for new antibacterial agents. Endophytic microorganisms are a promising alternative for drug discovery, as they produce a vast number of metabolites with unique characteristics and bioactive potential. This review highlights the importance of endophytic microorganisms as a source of secondary metabolites against medically important bacteria, particularly gram-negative species. The findings presented in this review provide 166 molecules with characterized chemical structures and antibacterial activities. Additionally, the low cost, ease of maintenance, and optimization-controlled fermentation conditions support reproducibility at a commercial scale.
Review
Engineering, Environmental
Meera Varghese, Manoj Balachandran
Summary: CDs, known for their nontoxic characteristics and inherent antibacterial potency, have gained significant attention as potential alternative antibiotics due to the increasing antibiotic resistance of bacterial strains. The light-driven antibacterial action of CDs is safe and effective with minimal side effects, and their direct interaction with bacterial cells contributes to their overall antibacterial activity. The unique and complex mechanisms of antibacterial activity of CDs involve ROS generation, degeneration of cell structure, and cytoplasm leakage, among other factors, providing insights for significant future research in this area.
JOURNAL OF ENVIRONMENTAL CHEMICAL ENGINEERING
(2021)
Article
Biochemistry & Molecular Biology
Boris Veltman, Dorin Harpaz, Yael Cohen, Elena Poverenov, Evgeni Eltzov
Summary: Chitosan nanoparticles modified with N-alkylamines exhibit selective binding properties to Gram-negative bacteria, leading to bacterial aggregation. Shorter chain length substituents on the modified CNPs result in higher aggregation effects, particularly towards Escherichia coli and Salmonella. Additionally, CNPs with lower degree of substitution show greater inhibitory effects on the growth of Gram-negative strains.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Infectious Diseases
Ze-Hua Cui, Hui-Ling He, Zi-Jian Zheng, Zhao-Qi Yuan, Ying Chen, Xin-Yi Huang, Hao Ren, Yu-Feng Zhou, Dong-Hao Zhao, Liang-Xing Fang, Yang Yu, Ya-Hong Liu, Xiao-Ping Liao, Jian Sun
Summary: Phentolamine enhances the antibacterial activity of macrolide antibiotics against Gram-negative bacteria by reducing efflux pump activity and causing direct damage to the outer membrane leaflet.
Article
Nanoscience & Nanotechnology
Megan A. Laune, Syed Ahad Zahidi, Jared T. Wiemann, Yan Yu
Summary: Nanosized liposomes can enhance the potency of antibiotics by fusing with bacterial membranes, but the interaction mechanisms are poorly understood. The fusion interactions between cationic liposomes and Escherichia coli were found to be heterogeneous, resulting in different antibacterial outcomes.
ACS APPLIED NANO MATERIALS
(2022)
Article
Materials Science, Biomaterials
Li Su, Sainan Qin, Xinai Yu, Yifei Chen, Liang Wang, Wenpei Dong, Zhongjian Xie, Han Zhang
Summary: Bacterial infections, especially Gram-negative ones, have become a growing problem due to antibiotic resistance. Nanozymes offer a promising solution by using reactive oxygen species (ROS) to kill bacteria. In this study, NiCo layered double hydroxide (LDH) nanozymes were synthesized and shown to selectively kill Gram-negative bacteria through their peroxide-like (POD-like) activity. Ni4Co6 LDHs exhibited the highest POD and antibacterial activity, and were able to selectively sterilize Gram-negative bacteria through electrostatic adsorption and hydrophilic interactions with the bacterial cell wall. Animal experiments demonstrated effective healing of G(-) bacteria-infected wounds without harming normal tissues. This research provides a new direction for the application of nanozymes.
JOURNAL OF MATERIALS CHEMISTRY B
(2023)
Article
Infectious Diseases
Jose Raul Nieto-Saucedo, Luis Esau Lopez-Jacome, Rafael Franco-Cendejas, Claudia Adriana Colin-Castro, Melissa Hernandez-Duran, Luis Raul Rivera-Garay, Karina Senyase Zamarripa-Martinez, Juan Luis Mosqueda-Gomez
Summary: The prevalence of carbapenem-resistant Gram-negative bacilli (CR-GNB) and the frequency of carbapenemase-encoding genes were evaluated in a tertiary referral center in El Bajio, Mexico. Among 508 Gram-negative bacilli, 37 were carbapenem-resistant (7.3%), and only 15 (40.5%) of them carried carbapenemase-encoding genes.
Review
Pharmacology & Pharmacy
Yuanhao Liu, Yunlong Lu, Zhongren Xu, Xiaoyan Ma, Xiuli Chen, Wukun Liu
Summary: Multidrug resistance is a significant issue in antibiotic clinical application, leading researchers to explore the potential of auranofin and other gold complexes as antibacterial agents. These advances offer a new perspective on the treatment of bacterial infections.
DRUG DISCOVERY TODAY
(2022)
Review
Immunology
Flora Cruz-Lopez, Adrian Martinez-Melendez, Rayo Morfin-Otero, Eduardo Rodriguez-Noriega, Hector J. Maldonado-Garza, Elvira Garza-Gonzalez
Summary: Infections caused by Gram-negative multi-drug resistant (MDR) bacterial species are difficult to treat due to widespread antibiotic resistance. New antibiotics and combinations with existing drugs have shown potential in treating these infections, but there are reports of resistance to these treatments.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Infectious Diseases
Qi Zhang, Shang Chen, Xiaojia Liu, Wenhan Lin, Kui Zhu
Summary: The combination of marine antibiotic equisetin and colistin shows a strong synergistic effect against Gram-negative bacteria, especially multi-drug resistant strains. Colistin promotes the intracellular accumulation of equisetin, leading to quick bacteria killing. Equisetin also restores colistin activity in an infection model, providing an alternative approach to combat Gram-negative pathogens in clinics.
Article
Infectious Diseases
Martina Traykovska, Robert Penchovsky
Summary: We described the design and application of a chimeric antisense oligonucleotide (ASO) called pVEC-ASO-1 as a novel antibacterial agent. By specifically degrading mRNA via RNase H, the pVEC-ASO-1 targets the S-adenosyl methionine (SAM)-I riboswitch found in Gram-positive bacteria, inhibiting bacterial growth.
Article
Biochemistry & Molecular Biology
Sara Lago, Matteo Nadai, Emanuela Ruggiero, Martina Tassinari, Maja Marusic, Beatrice Tosoni, Ilaria Frasson, Filippo M. Cernilogar, Valentina Pirota, Filippo Doria, Janez Plavec, Gunnar Schotta, Sara N. Richter
Summary: Well-differentiated liposarcoma is a malignant neoplasm characterized by amplification of the MDM2 gene region, and targeting the MDM2 G-quadruplex can promote apoptosis in cancer cells. The research suggests that this approach may be beneficial for treating WDLPS and other tumors seeking to restore wild-type p53.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Enrico Buglione, Domenico Salerno, Claudia Adriana Marrano, Valeria Cassina, Guglielmo Vesco, Luca Nardo, Mauro Dacasto, Riccardo Rigo, Claudia Sissi, Francesco Mantegazza
Summary: This study analyzed the nanomechanical properties of three G4s in the promoter of the KIT proto-oncogene using magnetic tweezers, identifying a characteristic fingerprint of G4 folding under negative supercoiling. It also examined the energetic contribution of G4 to the double-strand denaturation process and observed a reduction in the energy required for strands separation in the presence of negative supercoiling.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Guglielmo Vesco, Marco Lamperti, Domenico Salerno, Claudia Adriana Marrano, Valeria Cassina, Riccardo Rigo, Enrico Buglione, Maria Bondani, Giulia Nicoletto, Francesco Mantegazza, Claudia Sissi, Luca Nardo
Summary: Utilizing fluorescence resonance energy transfer, the folding of expressly designed constructs with G-quadruplexes flanked by double stranded DNA segments was investigated both in ensemble and at the single molecule level. The presence of flanking ends was found to bias both the final equilibrium state and the folding kinetics of the G-quadruplexes. This previously unconsidered aspect sheds light on the complex relationships involved in fine tuning the gene-regulatory properties of DNA structures.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Medicinal
Alberto Ongaro, Giovanni Desiderati, Erika Oselladore, Davide Auricchio, Maurizio Memo, Giovanni Ribaudo, Claudia Sissi, Alessandra Gianoncelli
Summary: This study found that guanine-rich sequences can form G-quadruplex structures in oncogenes and telomeres, inhibiting immortalization of cancer cells. Researchers improved ligand design based on an anthraquinone scaffold using click chemistry to enhance side chain length and interactions with nucleobases, leading to increased stability and selectivity towards G4 DNA.
Review
Biochemistry & Molecular Biology
Ilaria Frasson, Valentina Pirota, Sara N. Richter, Filippo Doria
Summary: G-quadruplexes (G4s) are stable non-canonical structures in human cells that regulate key cellular processes. They can form high-order structures through multimerization, and play important roles in genome replication, transcription, and translation.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Ilaria Caputo, Brasilina Caroccia, Ilaria Frasson, Elena Poggio, Stefania Zamberlan, Margherita Morpurgo, Teresa M. Seccia, Tito Cali, Marisa Brini, Sara N. Richter, Gian Paolo Rossi
Summary: Blockers of the renin-angiotensin system (RAS) can increase the expression of ACE2, the cellular receptor of SARS-CoV-2, and thus increase the risk of COVID-19. This study found that angiotensin II (Ang II) significantly increased the levels of ACE2 expression by acting on the angiotensin type 1 receptor, resulting in enhanced viral entry into cells. However, the blockade of ACE-1-mediated Ang II formation and ACE2-mediated Ang II conversion did not have any effect. Therefore, increased production of Ang II in patients with an activated RAS may lead to a greater spread of COVID-19 infection in lung cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Emanuela Ruggiero, Ilaria Frasson, Elena Tosoni, Matteo Scalabrin, Rosalba Perrone, Maja Marusic, Janez Plavec, Sara N. Richter
Summary: The fused in liposarcoma (FUS) protein has been found to selectively bind and stabilize the least stable and bulged G-quadruplex (G4) structure in HIV-1 LTR, leading to down-regulation of viral transcription. This study reveals the complexity and dynamics of HIV-1 LTR G4s, highlighting their significance as potential targets for antiviral therapies.
ACS INFECTIOUS DISEASES
(2022)
Review
Biochemistry & Molecular Biology
Massimiliano Berretta, Vincenzo Quagliariello, Alessia Bignucolo, Sergio Facchini, Nicola Maurea, Raffaele Di Francia, Francesco Fiorica, Saman Sharifi, Silvia Bressan, Sara N. Richter, Valentina Camozzi, Luca Rinaldi, Carla Scaroni, Monica Montopoli
Summary: This review examines the effects of vitamin D on human health, focusing particularly on its antioxidant and anti-inflammatory effects against cancer, immune-related diseases, cardiomyopathies, and infectious diseases. The study found that vitamin D significantly reduces the risk factors associated with chronic cardiometabolic disease and cancer.
Article
Chemistry, Medicinal
Roberta Rocca, Francesca Scionti, Matteo Nadai, Federica Moraca, Annalisa Maruca, Giosue Costa, Raffaella Catalano, Giada Juli, Maria Teresa Di Martino, Francesco Ortuso, Stefano Alcaro, Pierosandro Tagliaferri, Pierfrancesco Tassone, Sara N. Richter, Anna Artese
Summary: This study investigated the stabilizing effect of three candidate compounds on TERRA G4 through molecular modeling simulations, in vitro, and in cell analysis. The results demonstrated the stabilizing power of these candidates on TERRA G4, and they also showed good antiproliferative activity against colorectal and lung adenocarcinoma cell lines. This research could potentially provide new tools for cancer treatment.
Editorial Material
Biochemistry & Molecular Biology
Manlio Palumbo, Claudia Sissi
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Ilaria Frasson, Paola Solda, Matteo Nadai, Martina Tassinari, Matteo Scalabrin, Vijay Gokhale, Laurence H. Hurley, Sara N. Richter
Summary: A series of new quindoline-derivatives were evaluated, showing high binding to and stabilization of viral G4s. They exhibited nanomolar-range anti-HSV-1 activity in human cells with negligible cytotoxicity, demonstrating remarkable selectivity. These quindoline-derivatives emerge as a new class of G4 ligands with potent dual anti-HSV-1 activity.
ANTIVIRAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Giulia Nicoletto, Sara N. Richter, Ilaria Frasson
Summary: This study reports the presence, conservation, and localization of putative G4-forming sequences (PQSs) in human arboviruses. Analysis revealed that positive-strand ssRNA arboviruses, especially Flaviviruses, are enriched in highly conserved PQSs located in coding sequences (CDSs) or untranslated regions (UTRs), while negative-strand ssRNA and dsRNA arboviruses contain few conserved PQSs. The presence of highly conserved PQSs in human arboviruses highlights the potential of non-canonical nucleic acid structures as therapeutic targets in arbovirus infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Irene Zanin, Emanuela Ruggiero, Giulia Nicoletto, Sara Lago, Ilaria Maurizio, Irene Gallina, Sara N. Richter
Summary: Among the alternative secondary structures to the DNA double helix, i-Motifs (iMs) and G-quadruplexes (G4s) are non-canonical nucleic acid structures that form in cytosine- and guanine-rich regions, respectively. It was previously believed that iMs only form in vitro, but now it has been shown that they also form in live human cells, mainly at gene promoters. iMs and G4s have distinct activity as regulators of the cell transcriptome, with iMs associated with low transcript levels and G4s associated with high levels.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
