Article
Chemistry, Medicinal
M. Shaheer Malik, Shaikh Faazil, Meshari A. Alsharif, Qazi Mohammad Sajid Jamal, Jabir H. Al-Fahemi, Amrita Banerjee, Arpita Chattopadhyay, Samir Kumar Pal, Ahmed Kamal, Saleh A. Ahmed
Summary: The increasing bacterial resistance to common antibiotics necessitates the development of new antibacterial drugs urgently. In this study, we evaluated the antibacterial potential of novel oxazolidinone-sulphonamide/amide conjugates reported by our research group. Results showed that oxazolidinones 2 and 3a exhibited excellent potency against B. subtilis and P. aeruginosa strains, along with good antibiofilm activity. Docking studies and molecular dynamics simulations confirmed the higher binding affinities of these oxazolidinones compared to linezolid. Additionally, computational studies and ADME-T analysis demonstrated the potential of these novel linezolid-based oxazolidinones for further research.
Article
Infectious Diseases
Marzia Cinthi, Sonia Nina Coccitto, Simona Fioriti, Gianluca Morroni, Serena Simoni, Carla Vignaroli, Chiara Francesca Magistrali, Elisa Albini, Andrea Brenciani, Eleonora Giovanetti
Summary: This study investigates the genetic elements and transferability of linezolid resistance genes in enterococci from manure in a swine farm in Italy. The study found that these enterococci carry both cfr(D) and poxtA2 genes, which are located on a plasmid that is similar to a transposon in Staphylococcus aureus. The presence of these genes in swine manure highlights the importance of control measures to prevent their spread to other species.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Review
Immunology
Sarah B. Doernberg, Cesar A. Arias, Deena R. Altman, Ahmed Babiker, Helen W. Boucher, C. Buddy Creech, Sara E. Cosgrove, Scott R. Evans, Vance G. Fowler Jr, Stephanie A. Fritz, Toshimitsu Hamasaki, Brendan J. Kelly, Sixto M. Leal Jr, Catherine Liu, Thomas P. Lodise, Loren G. Miller, Jose M. Munita, Barbara E. Murray, Melinda M. Pettigrew, Felicia Ruffin, Marc H. Scheetz, Bo Shopsin, Truc T. Tran, Nicholas A. Turner, Derek J. Williams, Smitha Zaharoff, Thomas L. Holland
Summary: The Antibacterial Resistance Leadership Group (ARLG) has prioritized gram-positive bacterial infections as one of its scientific priorities. This article summarizes the accomplishments and future directions of ARLG studies on gram-positive infections.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Chemistry, Multidisciplinary
Musaed Alkholief, Mohd Abul Kalam, Abdullah K. Alshememry, Raisuddin Ali, Sulaiman S. Alhudaithi, Nasser B. Alsaleh, Mohammad Raish, Aws Alshamsan
Summary: Linezolid-loaded chitosan nanoparticles were developed for the topical treatment of bacterial eye infections. The nanoparticles showed sustained drug release and enhanced antibacterial activity compared to the free drug.
Article
Biochemistry & Molecular Biology
Shaik Faazil, M. Shaheer Malik, Saleh A. Ahmed, Reem I. Alsantali, Poornachandra Yedla, Meshari A. Alsharif, Iqbal N. Shaikh, Ahmed Kamal
Summary: The study presented a series of linezolid-based oxazolidinone compounds with potent anti-candidiasis and antitubercular activities, which were found to inhibit ergosterol biosynthesis pathway and tubercular growth effectively.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Sukhbayar Gankhuyag, Dong Sik Bae, Kyoung Lee, Seunghyun Lee
Summary: In this study, silica-supported Ag NPs (SiO2@Ag) were synthesized as effective antibacterial agents through a wet-impregnation method. The TEM analysis confirmed the formation of SiO2@Ag with excellent antibacterial activity against E. coli bacteria at a concentration up to 1.00 mg/mL, fully inhibiting bacterial growth. The obtained material also showed good adhesion to steel and polyethylene substrates, with high inhibition effect against E. coli bacteria.
Review
Chemistry, Medicinal
Qidi Kong, Yushe Yang
Summary: Antimicrobial resistance poses a global challenge as the effectiveness of old antibiotics diminishes. Discovery and development of antibacterial agents have been accelerated to replenish the limited and shrinking arsenal of antibiotics. Significant advances have been made in recent years in the antibacterial field, including new compounds of known classes and new compounds with new mechanisms.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Infectious Diseases
Loren Dejoies, Mohamed Sassi, Sacha Schutz, Julie Moreaux, Asma Zouari, Sophie Potrel, Anais Collet, Maxime Lecourt, Gabriel Auger, Vincent Cattoir
Summary: The study revealed the prevalence of poxtA gene in clinical enterococci in France since 2016, mostly in E. faecium and independently from optrA. Plasmids carrying poxtA also often co-carried resistance genes to phenicols and tetracyclines, potentially co-selected through veterinary use.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Chemistry, Medicinal
Jia Jiang, Yunlei Hou, Meibo Duan, Baihang Wang, Yachuang Wu, Xiudong Ding, Yanfang Zhao
Summary: Novel oxazolidinone derivatives with nitrogen-containing fused heterocyclic moiety were synthesized, and compound 3b showed significant antibacterial activity against S. aureus, indicating it as a promising drug candidate for further investigation.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Pharmacology & Pharmacy
Roberto Oliva, Giovanna Ginestra, Anna Piperno, Antonino Mazzaglia, Antonia Nostro, Angela Scala
Summary: This study developed a novel PLA-PEG NPs for the delivery of Linezolid against MRSA. The encapsulation efficiency of LNZ in PLA-PEG NPs was 15% with a 10:3 polymer to drug mass ratio, and sustained release kinetics with 65% of the antibiotic released within 80 h. The NPs exhibited antimicrobial activity against various Gram-positive bacteria including MRSA, and showed inhibitory activity on both planktonic growth and preformed biofilm of MRSA.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Infectious Diseases
Rafael Canton, Thomas Gottlieb, Geoffrey W. Coombs, Patrick C. Y. Woo, Tony M. Korman, Maria Garcia-Castillo, Denise Daley, Karri A. Bauer, Michael Wong, Dominik J. Wolf, Fakhar Siddiqui, Mary Motyl
Summary: Antimicrobial resistance (AMR) is a major global public health threat, particularly affecting patients in resource-poor settings. Various surveillance programs exist worldwide, and one of the largest is the SMART program, which has been running for 20 years. The SMART database includes data from nearly 500,000 isolates from over 60 countries, and can help monitor and guide clinical treatment.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
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)
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
Chemistry, Medicinal
Dmitry A. Makarov, Sergey D. Negrya, Maxim V. Jasko, Inna L. Karpenko, Pavel N. Solyev, Vladimir O. Chekhov, Dmitry N. Kaluzhny, Olga V. Efremenkova, Byazilya F. Vasilyeva, Alexander O. Chizhov, Darya A. Avdanina, Alexander A. Zhgun, Sergey N. Kochetkov, Liudmila A. Alexandrova
Summary: The emergence of drug-resistant strains of pathogenic microorganisms necessitates the creation of new drugs. In this study, a series of uridine derivatives with extended substituents at the C-5 position were obtained and their antimicrobial properties and solubility were explored. It was found that these new ribonucleoside derivatives have significantly higher solubility in water than their 2'-deoxy analogues and effectively inhibit the growth of several drug-resistant Gram-positive bacteria.
Article
Chemistry, Multidisciplinary
Xiaofeng Wu, Mengyao Yang, Ji Seon Kim, Rui Wang, Gyoungmi Kim, Jeongsun Ha, Heejeong Kim, Yejin Cho, Ki Taek Nam, Juyoung Yoon
Summary: Selective photodynamic agents can be designed based on reactive differences to treat Gram-positive bacterial infections. Sulfur-replaced phenoxazinium generates a superoxide anion radical that selectively kills Gram-positive bacteria, while selenium-substituted phenoxazinium produces singlet oxygen that can kill both Gram-positive and Gram-negative bacteria.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
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)