Article
Chemistry, Medicinal
Iris Cadima-Couto, Alexandra Tauzin, Joao M. Freire, Tiago N. Figueira, Ruben D. M. Silva, Clara Perez-Peinado, Catarina Cunha-Santos, Ines Bartolo, Nuno Taveira, Lurdes Gano, Joao D. G. Correia, Joao Goncalves, Fabrizio Mammano, David Andreu, Miguel A. R. B. Castanho, Ana Salome Veiga
Summary: The anti-HIV-1 peptide pepRF1, derived from the Dengue virus capsid protein, shows promising inhibitory effects with a potential therapeutic window higher than 53,000. It specifically targets CXCR4-tropic strains, preventing viral entry into target cells by acting as an antagonist of the viral coreceptor CXCR4. Compared to T20, a peptide-based HIV-1 entry inhibitor, pepRF1 is more effective and can potentially be used alone or in combination with other anti-HIV drugs, as well as a novel therapeutic strategy for other CXCR4-related diseases.
ACS INFECTIOUS DISEASES
(2021)
Review
Infectious Diseases
Maria Marinescu
Summary: Bacterial infections have become a major concern for researchers due to their increasing diversity and resistance to antibiotics. The emergence of SARS-CoV-2 infection has led to intensified research on finding new compounds with antimicrobial and antiviral properties. This review summarizes the synthesis methods of benzimidazole-triazole hybrids and their antimicrobial and antiviral activities, as well as the structure-activity relationship reported in the literature.
Article
Biochemistry & Molecular Biology
Mastaneh Safarnejad Shad, Sandra Claes, Eline Goffin, Tom Van Loy, Dominique Schols, Steven De Jonghe, Wim Dehaen
Summary: The expansion of the structure-activity relationship study of CXCR4 antagonists led to the synthesis of a series of isoquinolines with excellent activity, among which compound 24c showed consistently low nanomolar activity in various assays and was deemed the most promising.
Article
Biochemistry & Molecular Biology
Anja Bec, Maja Cindric, Leentje Persoons, Mihailo Banjanac, Vedrana Radovanovic, Dirk Daelemans, Marijana Hranjec
Summary: In this study, novel N-substituted benzimidazole-derived Schiff bases were designed and synthesized, and their antiviral, antibacterial, and antiproliferative activity were evaluated. The effects of substituents at the N atom of the benzimidazole nuclei and the type of substituents attached at the phenyl ring on the biological activity were investigated. The synthesized Schiff bases were tested for their antiviral activity against different viruses, antibacterial activity against various bacterial strains, and antiproliferative activity on human cancer cell lines, revealing the structure activity relationships. Several compounds showed mild antiviral effects, while some derivatives exhibited moderate antibacterial activity. One particular Schiff base, 4-N,N-diethylamino-2-hydroxy-substituted derivative with a phenyl ring at the N atom on the benzimidazole nuclei, displayed a strong antiproliferative activity against cancer cell lines, especially acute myeloid leukemia (HL-60).
Review
Gastroenterology & Hepatology
Francesco Paolo Russo, Mauro Vigano, Peter Stock, Alberto Ferrarese, Nicola Pugliese, Patrizia Burra, Alessio Aghemo
Summary: Organ transplantation is a life-saving treatment for patients with end-stage organ disease, but it is limited by a shortage of available organs. In recent years, there have been explorations and attempts to transplant organs from HBV and HIV positive donors in some countries. However, post-transplant antiviral therapies are necessary to prevent virus reactivation, and intentional virus transmission has practical, ethical, and clinical implications.
JOURNAL OF HEPATOLOGY
(2022)
Article
Immunology
Xiaoyan Hu, Yi Feng, Kang Li, Yueyang Yu, Abdur Rashid, Hui Xing, Yuhua Ruan, Lingling Lu, Min Wei, Yiming Shao
Summary: CRF07_BC is a prevalent HIV-1 strain in China, characterized by predominantly single CCR5 tropism. This study found evidence that CRF07_BC has the ability to evolve into CXCR4 strains.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Chunfu Wang, Haichang Huang, Kirsten Mallon, Lourdes Valera, Kyle Parcella, Mark I. Cockett, John F. Kadow, Eric P. Gillis, Mark Krystal, Robert A. Fridell
Summary: GSK878 is a potent inhibitor of HIV-1 that binds to the CA hexamer. It shows high efficacy against HIV-1 and variants with diverse CA sequences. Mechanism studies reveal that GSK878 blocks early and late steps of HIV-1 replication, primarily through altered stability of the HIV-1 CA core.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Chemistry, Organic
N. Jeelan Basha
Summary: This review provides an overview of the synthesis of benzimidazole analogs and explores the recent research on benzimidazole analogs designed as antibacterial, antifungal, anticancer, and antiviral agents.
POLYCYCLIC AROMATIC COMPOUNDS
(2023)
Article
Biochemistry & Molecular Biology
Ping Gao, Shu Song, Zhao Wang, Lin Sun, Jian Zhang, Christophe Pannecouque, Erik De Clercq, Peng Zhan, Xinyong Liu
Summary: Novel diarylpyrimidine derivatives designed and synthesized in the study demonstrated strong anti-HIV activity, with compounds IVB-5-4 and IVB-5-8 showing superior activity against HIV-1(IIIB). These compounds not only exhibited potent inhibition against wide-type HIV-1 strain, but also showed low nanomole activity against some mutant strains.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Migara Kavishka Jayasinghe, Marco Pirisinu, Yuqi Yang, Boya Peng, Thach Tuan Pham, Chang Yu Lee, Melissa Tan, Luyen Tien Vu, Xuan T. T. Dang, Tin Chanh Pham, Huan Chen, Anskar Y. H. Leung, William C. Cho, Jiahai Shi, Minh T. N. Le
Summary: The use of extracellular vesicles (EVs) as drug delivery vectors has gained attention due to their ability to efficiently deliver therapeutic payloads to diseased cells. Surface functionalization methods have been developed to enhance the stability and biocompatibility of EVs, allowing for targeted delivery to cancer cells and improved metastasis suppression. Extensive testing has shown that engineered EVs are biocompatible and safe for repeated dose treatment.
Review
Immunology
Lina S. M. Huang, Evan Y. Snyder, Robert T. Schooley
Summary: AIDS caused by HIV-1 has been a global public health challenge for decades. While drugs targeting CCR5-mediated entry or HIV-1 replication have been used clinically, drugs targeting CXCR4 have not yet reached clinical application. Research is ongoing on discovering novel molecules targeting CXCR4 for potential future anti-HIV therapeutic development.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Immunology
Dang-Nghiem Vo, Nicolas Leventoux, Mauricio Campos-Mora, Sandrine Gimenez, Pierre Corbeau, Martin Villalba
Summary: NK cells play a critical role in the antiviral immune response against HIV-1. Impaired NK cell activity is observed in HIV-1 patients, with alterations in NK cell subsets and the emergence of memory NK cells. NK cells can acquire CCR5 and CXCR4 through trogocytosis from T cells, but not CD4. HIV-1 patients exhibit distinct NK cell clusters, with increased expression of CXCR4 and CCR5 in viremic patients. Degranulation and trogocytosis may be linked in HIV-1 infection.
Article
Biology
Chansavath Phetsouphanh, Prabhjeet Phalora, Carl-Philipp Hackstein, John Thornhill, C. Mee Ling Munier, Jodi Meyerowitz, Lyle Murray, Cloete VanVuuren, Dominique Goedhals, Linnea Drexhage, Rebecca Moore, Quentin J. Sattentau, Jeffrey Yw Mak, David P. Fairlie, Sarah Fidler, Anthony D. Kelleher, John Frater, Paul Klenerman
Summary: Human MAIT cells play a crucial role in HIV-1 infection by inhibiting viral replication and protecting the host from infection. They are activated by IL-12 and IL-18, leading to the release of various cytokines upon activation.
Article
Immunology
Lin He, Chen Wang, Yuanyuan Zhang, Huihui Chong, Xiaoyan Hu, Dan Li, Hui Xing, Yuxian He, Yiming Shao, Kunxue Hong, Liying Ma
Summary: This study suggests that Lipopeptide-19 exhibits potent anti-HIV activity against various subtype clinical isolates and has high drug resistance barrier.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Sara Moron-Lopez, Silvia Bernal, Joseph K. Wong, Javier Martinez-Picado, Steven A. Yukl
Summary: ABX464 has a significant effect on the HIV reservoir and transcription profile, decreasing total HIV DNA and HIV transcriptional initiation, and possibly decreasing intact HIV DNA and HIV transcriptional elongation.
CLINICAL INFECTIOUS DISEASES
(2022)
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)