Article
Chemistry, Multidisciplinary
Jessa Marie V. Makabenta, Ahmed Nabawy, Aritra Nath Chattopadhyay, Taewon Jeon, Jungmi Park, Pui Chi Lo, Stas Nosovitski, Rui Huang, Cheng-Hsuan Li, Mingdi Jiang, Vincent M. Rotello
Summary: Integration of antimicrobial polymeric nanoparticles into hydrogel materials provides a promising strategy for treating multidrug-resistant biofilm infections. This study demonstrates the efficacy and selectivity of an injectable hydrogel loaded with engineered cationic antimicrobial polymeric nanoparticles (PNPs) for the treatment of severe wound biofilm infections.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Engineering, Environmental
Yu-Jia Li, Shih-Chun Wei, Han-Wei Chu, Hong-Jyuan Jian, Anisha Anand, Amit Nain, Yu-Fen Huang, Huan-Tsung Chang, Chih-Ching Huang, Jui-Yang Lai
Summary: In this study, a novel nanoVelcro dressing made from quercetin (QNV) was developed, which exhibited antibacterial, anti-oxidative, and anti-inflammatory effects, as well as endotoxin neutralization. The dressing effectively inhibited the growth of various bacteria and accelerated wound closure rate in infected wounds.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Dermatology
Ameyo M. Dorkenoo, Akovi K. Adjetey-Toglozombio, Bright K. Ocansey, Efoe Sossou, Fiali Lack, David W. Denning
Summary: This study estimated the burden of serious fungal infections in Togo and highlighted the significance of these infections, which may be more significant than expected. The findings underscored the need to increase awareness among healthcare professionals, enhance diagnostic and therapeutic capacities, and intensify epidemiological studies for effective management of fungal infections in Togo.
Review
Pharmacology & Pharmacy
Eve W. L. Chow, Li Mei Pang, Yue Wang
Summary: Many human fungal pathogens are opportunistic, becoming infectious when the host's immunity and microbiome are compromised. Bacteria in the human microbiome play a crucial role in keeping fungi harmless and defending against fungal infection. The Human Microbiome Project has significantly advanced our understanding of the interaction between bacteria and fungi, providing insights for developing antifungal strategies.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Review
Microbiology
Ang Hu, Zeming Hu, Haohong Zou, Jiankang Zhang, Dongliang Zhang, Hao Wang, Jianing Zhong, Bin Chen
Summary: This article reviews recent clinical and basic studies on the mechanism and function of CARD9, a crucial mediator in fungal, bacterial, viral, and parasitic infections. The article also summarizes the latest treatment and prevention strategies based on CARD9 and discusses the current perspectives and future directions of CARD9.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Qonita Kurnia Anjani, Akmal Hidayat Bin Sabri, Aaron J. Hutton, Alvaro Carcamo-Martinez, Luki Ahmadi Hari Wardoyo, Alvanov Zpalanzani Mansoor, Ryan F. Donnelly
Summary: Since the 1970s, research on micro array patches (MAPs) for drug delivery has advanced from simple solid patches to bio responsive systems. In addition to improving transdermal drug delivery, there is growing interest in using MAPs to manage infectious diseases. MAPs offer a minimally invasive and self-administered solution, and they can also be used as biosensors for disease diagnosis. This review aims to analyze the potential utility of MAPs in managing infectious diseases such as tuberculosis, skin infections, malaria, methicillin-resistant Staphylococcus aureus infections, and Covid-19, and discuss their efficacy and limitations.
JOURNAL OF CONTROLLED RELEASE
(2023)
Review
Biochemistry & Molecular Biology
Antonin C. Andre, Matthieu Laborde, Benoit S. Marteyn
Summary: Pathogens face hypoxia during infection, which affects the interaction between host immune cells and pathogens. Hypoxia dampens the antimicrobial activities of immune cells and modulates pathogen virulence, promoting their dissemination. Further research is needed to understand the importance of oxygen in pathogen invasion and colonization and to develop innovative therapeutic strategies.
TRENDS IN MICROBIOLOGY
(2022)
Review
Infectious Diseases
Olga M. Tsivileva, Oleg Koftin, Nina Evseeva
Summary: Coumarin derivatives have wide practical application and unique reactivity. More than 1300 coumarins have been identified in plants, bacteria, and fungi. Fungal coumarins, with their promising therapeutic potential in fields such as cancer and microbial infections, deserve further study.
Article
Infectious Diseases
Srinivas Reddy Pallerla, Darrel Ornelle Elion Assiana, Le Thi Kieu Linh, Frederick Nchang Cho, Christian G. Meyer, Kaossarath Adedjoke Fagbemi, Ayola Akim Adegnika, Veronique Penlap Beng, Eric A. Achidi, Gauthier Mesia Kahunu, Mathew Bates, Martin P. Grobusch, Peter G. Kremsner, Francine Ntoumi, Thirumalaisamy P. Velavan
Summary: The study revealed significant differences in allele frequencies of pharmacogenetic variants between the Republic of Congo and non-African populations, with fewer differences observed when compared to other African populations. Additionally, considerable diversity in allele frequencies of pharmacogenetic variants among African populations was noted.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2021)
Review
Immunology
Pratibha Gaur, Ilan Zaffran, Tresa George, Fidan Rahimli Alekberli, Micha Ben-Zimra, Francesca Levi-Schaffer
Summary: This review summarizes updated information on the direct and indirect interactions of eosinophils with pathogens. Eosinophils, traditionally associated with allergic and parasitic diseases, have been shown to play a role in maintaining homeostasis and fighting infectious diseases. They possess various cellular mechanisms to combat pathogens and contribute to an efficient immune response.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2022)
Review
Microbiology
Bassey E. Ekeng, Adeyinka A. Davies, Iriagbonse I. Osaigbovo, Adilia Warris, Rita O. Oladele, David W. Denning
Summary: Fungal infections often present with symptoms that closely resemble other clinical entities, particularly tuberculosis. This review identifies several fungal infections, including histoplasmosis, aspergillosis, and blastomycosis, that can mimic tuberculosis. The study highlights the importance of considering and ruling out these fungal infections when a patient presents with tuberculosis-like symptoms.
Review
Infectious Diseases
Luis Alberto Ribeiro Froes, Tereza Setsuko Toma, Marie Jachiet, Laurie Rousset, Rosana Evangelista Poderoso, Maria Angela Bianconcini Trindade
Summary: Our review summarizes the clinical and epidemiological characteristics of non-viral co-infections in leprosy patients. Male-dominated pattern of co-infections among working-age individuals with multibacillary leprosy was observed and co-infections with tuberculosis and leishmaniasis appeared to reduce leprosy reactions.
PLOS NEGLECTED TROPICAL DISEASES
(2023)
Review
Gastroenterology & Hepatology
Phillipp Hartmann, Bernd Schnabl
Summary: Liver and biliary diseases have a significant impact on global health, with the intestinal bacterial microbiome playing a well-established role. However, the role of the fungal microbiome, or mycobiome, has been overlooked for a long time. Recent studies have highlighted the importance of the mycobiome in hepatobiliary diseases, particularly the involvement of the Candida genus. This article compares colonization and infection, describes mycobiome findings in healthy and diseased states, and discusses the potential for modulating the gut mycobiome to improve hepatobiliary conditions.
JOURNAL OF HEPATOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Paul A. Agius, Julia C. Cutts, Peige Song, Igor Rudan, Diana Rudan, Victor Aboyans, Mary M. McDermott, Michael H. Criqui, F. Gerald R. Fowkes, Freya J. Fowkes
Summary: An epidemiological transition is occurring in the prevalence of peripheral artery disease (PAD), particularly in low- and middle-income countries (LMICs) due to an aging population and western lifestyle adoption. Limited evidence suggests that infection, potentially mediated by inflammation, may be a risk factor for PAD. An ecological analysis also shows a correlation between country-level prevalence of major endemic infections and PAD prevalence.
JOURNAL OF EPIDEMIOLOGY AND GLOBAL HEALTH
(2022)
Article
Multidisciplinary Sciences
Joel A. Finbloom, Preethi Raghavan, Michael Kwon, Bhushan N. Kharbikar, Michelle A. Yu, Tejal A. Desai
Summary: Researchers have developed a nanoscale drug carrier that can deliver both antibiotics and antimicrobial silver nanoparticles to bacterial infections, showing synergistic antimicrobial effects against Pseudomonas aeruginosa. The carrier has also demonstrated positive outcomes in reducing bacterial burden and improving survival outcomes in a mouse model of lung infection.
Review
Biochemistry & Molecular Biology
Silvia Anselmi, Nandini Aggarwal, Thomas S. Moody, Daniele Castagnolo
Summary: Sulfoxides, important organic compounds widely used in pharmaceutical and organic chemistry, can be synthesized enantioenriched through various biocatalytic approaches. Recent advances include the use of reductive enzymes and unconventional solvents, such as ionic liquids and deep eutectic solvents, for greener and more sustainable synthetic pathways.
Article
Chemistry, Medicinal
Anita Toscani, Charlotte Hind, Melanie Clifford, Seong-Heun Kim, Antonia Gucic, Charlotte Woolley, Naima Saeed, Khondaker Miraz Rahman, J. Mark Sutton, Daniele Castagnolo
Summary: The study reports the synthesis and biological evaluation of a series of phenanthroline-based visible-light-activated manganese(I) carbon-monoxide-releasing molecules (PhotoCORMs) against ESKAPE bacteria and bacterial biofilms. These PhotoCORMs release CO under blue light irradiation and show effective antibacterial activity against multidrug-resistant bacteria, with potential applications in combating antimicrobial resistance.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Anita Toscani, Rossana Denaro, Sergio Fernando Castillo Pacheco, Matteo Biolatti, Silvia Anselmi, Valentina Dell'Oste, Daniele Castagnolo
Summary: A series of amidinourea compounds have been synthesized as potential non-nucleoside anti-HSV agents, showing micromolar activity against HSV-1 with low cytotoxicity. These compounds act in an early stage of the HSV replication cycle, just after viral attachment and entry.
Article
Chemistry, Medicinal
Dorothy Semenya, Meir Touitou, Camila Maringolo Ribeiro, Fernando Rogerio Pavan, Luca Pisano, Vinayak Singh, Kelly Chibale, Georg Bano, Anita Toscani, Fabrizio Manetti, Beatrice Gianibbi, Daniele Castagnolo
Summary: A series of indolyl-3-methyleneamines were designed and synthesized for investigation as new chemical entities against Mycobacterium tuberculosis (Mtb). Compound 7j displayed potent activity and may inhibit Mtb through a unique mechanism.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Fei Zhao, Kate Lauder, Siyu Liu, James D. Finnigan, Simon B. R. Charnock, Simon J. Charnock, Daniele Castagnolo
Summary: This study describes the development of novel biocatalytic and chemoenzymatic methods for the enantioselective synthesis of chiral beta-hydroxysulfides using ketoreductase enzymes. Four ketoreductases were discovered and isolated, enabling the synthesis of beta-hydroxysulfides with different configurations. By utilizing novel chemoenzymatic and biocatalytic reactions or dynamic kinetic resolution, high enantioselective synthesis was achieved using commercially available starting materials.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Medicinal
Guilherme F. S. Fernandes, Andrew M. Thompson, Daniele Castagnolo, William A. Denny, Jean L. Dos Santos
Summary: Tuberculosis (TB) has taken more lives than any other infectious disease in the past 2000 years. Despite the comparable death toll with COVID-19 in 2020, the World Health Organization emphasizes the need for new TB drugs to end this pandemic. However, only a small fraction of the promising anti-TB compounds reported annually successfully reach clinical development.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Dorothy Semenya, Meir Touitou, Domiziana Masci, Camila Maringolo Ribeiro, Fernando Rogerio Pavan, Guilherme Felipe Dos Santos Fernandes, Beatrice Gianibbi, Fabrizio Manetti, Daniele Castagnolo
Summary: The exploration around the 2,5-dimethylpyrrole scaffold of antitubercular hit compound 1 has led to the discovery of new derivatives that are active against Mycobacterium tuberculosis and multidrug-resistant clinical isolates. Some of these derivatives showed promising cytotoxicity profiles and were effective in inhibiting the growth of intracellular mycobacteria.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Silvia Anselmi, Alexandra T. P. Carvalho, Angela Serrano-Sanchez, Jose L. Ortega-Roldan, Jill Caswell, Iman Omar, Gustavo Perez-Ortiz, Sarah M. Barry, Thomas S. Moody, Daniele Castagnolo
Summary: This study identifies selective and robust MsrA biocatalysts capable of efficiently catalyzing enantioselective reduction of various aromatic and aliphatic chiral sulfoxides at concentrations of 8-64 mM with high yields and excellent enantiomeric excess (up to 99%). Through rational mutagenesis design using in silico docking, molecular dynamics, and structural nuclear magnetic resonance (NMR) studies, a mutant enzyme MsrA33 was developed, which can catalyze the kinetic resolution of bulky sulfoxide substrates with non-methyl substituents on the sulfur atom with enantiomeric excess up to 99%, overcoming a significant limitation of current MsrA biocatalysts.
Article
Chemistry, Physical
Haoyue Xiang, Salvatore Ferla, Carmine Varricchio, Andrea Brancale, Nicola L. Brown, Gary W. Black, Nicholas J. Turner, Daniele Castagnolo
Summary: Two enzymatic strategies were developed to oxidize 1,2,3,4-tetrahydroquinolines (THQs) and N-cyclopropyl-N-alkylanilines into quinolines and 2-quinolones, respectively. Whole cells and monoamine oxidase (MAO-N) enzymes were used for the biotransformation of THQs, while horseradish peroxidase (HRP)-catalyzed annulation/aromatization reaction followed by Fe-mediated oxidation was employed for the conversion of N-cyclopropyl-N-alkylanilines into 2-quinolone compounds.
Review
Biochemistry & Molecular Biology
Guilherme Felipe Santos Fernandes, Caue Benito Scarim, Seong-Heun Kim, Jingyue Wu, Daniele Castagnolo
Summary: Oxazolidinone is a five-member heterocyclic ring with diverse applications in medicinal chemistry. Among the isomers, 2-oxazolidinone has been extensively explored and numerous analogues have been developed. Despite promising pharmacological applications in various therapeutic areas, most oxazolidinone derivatives have not progressed beyond the initial stages of drug development. This review highlights the efforts of medicinal chemists in exploring this scaffold and emphasizes its potential for medicinal chemistry.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Silvia Anselmi, Siyu Liu, Seong-Heun Kim, Sarah M. Barry, Thomas S. Moody, Daniele Castagnolo
Summary: A mild, chemoselective and sustainable biocatalysed synthesis of sulfoxides has been developed with CALB and AcOEt, leading to high yields and excellent E-factors in the synthesis of a range of sulfoxides, including the drug omeprazole.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
