Letter
Medicine, General & Internal
S. Sean Tu, Sarosh Nagar, Aaron S. Kesselheim, Zhigang Lu, Benjamin N. Rome
Summary: This study assesses the sales revenue generated in the first five years for newly launched brand-name drugs, comparing those with and without an initial orphan drug designation.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2023)
Review
Pharmacology & Pharmacy
Frank W. Pun, Ivan V. Ozerov, Alex Zhavoronkov
Summary: Disease modeling and target identification are crucial in drug discovery, and artificial intelligence is increasingly being used in this field. This article reviews recent advances in AI-driven target discovery and discusses the importance of striking a balance between novelty and confidence in target selection. It also highlights the validation of AI-identified targets through experiments and the potential pathways for further development.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Chemistry, Medicinal
Run-Zhu Fan, Lin Chen, Tong Su, Wei Li, Jia-Luo Huang, Jun Sang, Gui-Hua Tang, Sheng Yin
Summary: In this study, a series of highly potent anti-TNBC small molecule compounds were isolated through bioassay-guided isolation, with 8,9-seco-ent-kaurane 6 showing promising activity and selectivity. The compounds may induce apoptosis, autophagy, and metastasis suppression in TNBC cells by inhibiting Akt, and demonstrate significant tumor growth suppression effects in vivo. These results suggest that these compounds hold potential for future development as novel anti-TNBC agents.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biotechnology & Applied Microbiology
Atanas G. Atanasov, Sergey B. Zotchev, Verena M. Dirsch, Claudiu T. Supuran
Summary: Natural products and their analogues have historically played a significant role in pharmacotherapy, however, they also present challenges. Recent technological and scientific developments are addressing these challenges and revitalizing interest in natural products as drug leads, particularly for combating antimicrobial resistance.
NATURE REVIEWS DRUG DISCOVERY
(2021)
Article
Biochemistry & Molecular Biology
Giuseppe Ermondi, Diego Garcia-Jimenez, Giulia Caron
Summary: The study utilized the PROTAC-DB database to gather information on PROTACs and building blocks, calculating 2D descriptors and using graphical tools to analyze and compare the chemical space. Results indicated that linkers have different properties than E3 ligands and warheads, and analysis of three PROTACs with varying permeability showed that the most permeable compounds exhibit different properties compared to bRo5 drugs. The study also discussed the relevance of physicochemical descriptors on degradation activity using the PROTACpedia database.
Review
Pharmacology & Pharmacy
Lu Wang, Yonghuan Yan, Linfang Wu, Jinyong Peng
Summary: With changing lifestyles, non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease worldwide. Natural products (NPs) have been found to have high activity and low side effects, making them an important source for the development of new drugs to treat NAFLD. Studies have shown that regulating lipid metabolism, insulin resistance, oxidative stress, and inflammation-related pathways may play important roles in the anti-NAFLD effects of NPs.
PHARMACOLOGICAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Paula Carracedo-Reboredo, Jose Linares-Blanco, Nereida Rodriguez-Fernandez, Francisco Cedron, Francisco J. Novoa, Adrian Carballal, Victor Maojo, Alejandro Pazos, Carlos Fernandez-Lozano
Summary: In recent years, machine learning techniques have been widely used in drug discovery to improve efficiency and reduce costs. To achieve the goals set by the Precision Medicine initiative, higher requirements have been proposed for the robustness, standardization, and reproducibility of computational methods.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Review
Chemistry, Medicinal
Amit Kumar, Ankit Siwach, Prabhakar Verma
Summary: Pyrimidine and its derivatives are important heterocyclic compounds with wide applications in medicinal chemistry. Pyrimidine plays a significant role as an organic reaction intermediate and exhibits diverse biological activities such as antibacterial and anti-inflammatory effects. Various methods have been reported for the synthesis of pyrimidine derivatives.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2022)
Review
Biotechnology & Applied Microbiology
Chun-Qiang Li, Hong-Mei Lei, Qian-Yi Hu, Guo-Hong Li, Pei-Ji Zhao
Summary: The review outlines recent advances in synthetic biology of natural drugs, focusing on optimization and reconstruction of biosynthetic pathways for mass production of certain drugs. The study provides new strategies for large-scale preparation of rare natural plant metabolites and highly bioactive microbial compounds. Additionally, it discusses the potential advantages and disadvantages of using synthetic biology and various expression systems for heterologous expression of natural drugs.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Plant Sciences
Yohei Morishita, Kento Tsukada, Kazuma Murakami, Kazuhiro Irie, Teigo Asai
Summary: Nine new diterpenoid pyrones, shearones A-I (1-9), were discovered from the fungus Eupenicillium shearii. Some of these compounds exhibited moderate antiaggregative ability against amyloid beta 42.
JOURNAL OF NATURAL PRODUCTS
(2022)
Review
Biochemistry & Molecular Biology
K. L. T. Dilrukshi Jayawardene, Enzo A. Palombo, Peter R. Boag
Summary: Parasitic nematodes infect a wide range of organisms and have significant impact on human health and agriculture. The main method of controlling these parasites is through anthelmintic drugs, but there is limited selection in the market and resistance is a major issue. Therefore, the development of new anthelmintics is crucial for sustainable parasitic control.
Review
Biochemistry & Molecular Biology
Younghoon Kim, Sandip Sengupta, Taebo Sim
Summary: The review discusses the anti-tumor activities and synthetic routes of natural and synthetic lactones, highlighting their potential as anticancer agents and aiming to advance the process of oncology drug discovery based on natural products.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biology
Hafsa Qadri, Abdul Haseeb Shah, Syed Mudasir Ahmad, Bader Alshehri, Abdullah Almilaibary, Manzoor Ahmad Mir
Summary: Human infectious diseases caused by microbial pathogens continue to be a major health issue. Antimicrobial-resistant pathogens have developed resistance to existing drugs, leading to an upsurge in drug-resistant microbial species during the COVID-19 outbreak. Natural antimicrobial compounds extracted from various sources, particularly plants, show promise in combating drug tolerance and resistance. This review provides a detailed analysis of these compounds and their potential mechanisms of action against pathogenic fungi and bacteria, offering insights for improving current antimicrobial treatments and addressing the rising number of bacterial and fungal infections.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Miroslava Nedyalkova, Vasil Simeonov
Summary: This study focuses on utilizing descriptors to build a partitioning model for the application of natural compounds in drug discovery, especially in dealing with severe diseases. The research emphasizes the importance of matching descriptors to natural compounds with diverse structures and complex actions towards deadly infectious diseases like the SARS-CoV-2 virus.
Review
Biochemistry & Molecular Biology
Junyang Wang, Jens Nielsen, Zihe Liu
Summary: A wide range of bacteria, fungi, and plants can produce bioactive secondary metabolites known as natural products. Advances in synthetic biology have provided new opportunities for the discovery of natural products.
Article
Substance Abuse
Jake W. O'Brien, Benjamin J. Tscharke, Richard Bade, Gary Chan, Cobus Gerber, Jochen F. Mueller, Kevin Thomas, Wayne D. Hall
Summary: After the implementation of a minimum unit alcohol price policy in the Northern Territory of Australia, there was a significant reduction in alcohol consumption, but consumption gradually recovered and almost returned to pre-policy levels over time.
Review
Radiology, Nuclear Medicine & Medical Imaging
Neil J. Stewart, Laurie J. Smith, Ho-Fung Chan, James A. Eaden, Smitha Rajaram, Andrew J. Swift, Nicholas D. Weatherley, Alberto Biancardi, Guilhem J. Collier, David Hughes, Gill Klafkowski, Christopher S. Johns, Noreen West, Kelechi Ugonna, Stephen M. Bianchi, Rod Lawson, Ian Sabroe, Helen Marshall, Jim M. Wild
Summary: The use of pulmonary MRI has been limited in clinical settings, but advancements in ultrashort and zero echo time MRI techniques have enabled non-ionising structural imaging in certain lung disorders. Hyperpolarised gas MRI with inhaled 3He and 129Xe, a complementary technique for functional and microstructural imaging of the lung, has great potential as a clinical tool for early detection and improved understanding of pathophysiology in various lung diseases. It can also enable safe and sensitive monitoring of disease progression and response to therapy.
BRITISH JOURNAL OF RADIOLOGY
(2022)
Article
Environmental Sciences
Aaron J. Pandopulos, Bradley S. Simpson, Jason M. White, Richard Bade, Cobus Gerber
Summary: The study evaluated the distribution of cannabis chemical markers in faeces and urine, and their impact on wastewater loads. THC-COOH was found to partition 40% in water, while CBD remained largely associated with the particulate fraction. Faecal loads from cannabis users and non-users affected the total measured amounts of cannabinoids in the aqueous phase.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Engineering, Environmental
Richard Bade, Jason M. White, Maulik Ghetia, Santosh Adiraju, Sangeet Adhikari, Lubertus Bijlsma, Tim Boogaerts, Daniel A. Burgard, Sara Castiglioni, Alberto Celma, Andrew Chappell, Adrian Covaci, Erin M. Driver, Rolf U. Halden, Felix Hernandez, Heon-Jun Lee, Alexander L. N. van Nuijs, Jeong-Eun Oh, Marco A. Pineda Castro, Noelia Salgueiro-Gonzalez, Bikram Subedi, Xue-Ting Shao, Viviane Yargeau, Ettore Zuccato, Cobus Gerber
Summary: This study focused on 28 NPS stimulants and detected 11 of them, with eutylone and 3-methylmethcathinone (3MMC) being the most commonly found and with the highest mass loads, indicating international popularity. Older generation stimulants like para-methoxyamphetamine (PMA), methylone, and mephedrone were also detected, showing the dynamic nature of the NPS market. Areas in New Zealand were found to have the highest loads of NPS stimulant consumption, demonstrating the potential public health risks associated with these substances.
ENVIRONMENTAL SCIENCE & TECHNOLOGY LETTERS
(2022)
Article
Critical Care Medicine
Ho-Fung Chan, Laurie J. Smith, Alberto M. Biancardi, Jody Bray, Helen Marshall, Paul J. C. Hughes, Guilhem J. Collier, Madhwesha Rao, Graham Norquay, Andrew J. Swift, Kylie Hart, Michael Cousins, W. John Watkins, Jim M. Wild, Sailesh Kotecha
Summary: This study aimed to investigate the associations between bronchopulmonary dysplasia (BPD) and lung function phenotypes on lung ventilation and microstructure in preterm-born children. The results showed that preterm-born children with POLD had increased ventilation abnormalities, while those with BPD had abnormal lung microstructure.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Environmental Sciences
Bradley S. Simpson, Emma L. Jaunay, Maulik Ghetia, Lynn Nguyen, Richard Bade, Jason M. White, Cobus Gerber
Summary: The low and persistent presence of methcathinone in wastewater in South Australia may arise from the oxidation of pseudoephedrine in the sewer system, rather than being solely used as a drug of choice.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Chemistry, Medicinal
Alberto Celma, Richard Bade, Juan Vicente Sancho, Felix Hernandez, Melissa Humphries, Lubertus Bijlsma
Summary: Ultra-high performance liquid chromatography coupled to ion mobility separation and high-resolution mass spectrometry instruments are valuable for screening emerging contaminants in the aquatic environment. However, in the absence of reference standards, the prediction of retention time (RT) and collision cross-section (CCS) values is important. This study developed Multiple Adaptive Regression Splines (MARS) prediction models for RT and CCS, which were validated using a database of protonated molecules, deprotonated molecules, and sodium adducts. The developed models, integrated in an open-access online platform, enable the prediction of both RT and CCS data.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Environmental Sciences
Hiba Mohammed Taha, Reza Aalizadeh, Nikiforos Alygizakis, Jean-Philippe Antignac, Hans Peter H. Arp, Richard Bade, Nancy Baker, Lidia Belova, Lubertus Bijlsma, Evan E. Bolton, Werner Brack, Alberto Celma, Wen-Ling Chen, Tiejun Cheng, Parviel Chirsir, L'ubos Cirka, Lisa A. D'Agostino, Yannick Djoumbou Feunang, Valeria Dulio, Stellan Fischer, Pablo Gago-Ferrero, Aikaterini Galani, Birgit Geueke, Natalia Glowacka, Juliane Gluge, Ksenia Groh, Sylvia Grosse, Peter Haglund, Pertti J. Hakkinen, Sarah E. Hale, Felix Hernandez, Elisabeth M-L Janssen, Tim Jonkers, Karin Kiefer, Michal Kirchner, Jan Koschorreck, Martin Krauss, Jessy Krier, Marja H. Lamoree, Marion Letzel, Thomas Letzel, Qingliang Li, James Little, Yanna Liu, David M. Lunderberg, Jonathan W. Martin, Andrew D. McEachran, John A. McLean, Christiane Meier, Jeroen Meijer, Frank Menger, Carla Merino, Jane Muncke, Matthias Muschket, Michael Neumann, Vanessa Neveu, Kelsey Ng, Herbert Oberacher, Jake O'Brien, Peter Oswald, Martina Oswaldova, Jaqueline A. Picache, Cristina Postigo, Noelia Ramirez, Thorsten Reemtsma, Justin Renaud, Pawel Rostkowski, Heinz Ruedel, Reza M. Salek, Saer Samanipour, Martin Scheringer, Ivo Schliebner, Wolfgang Schulz, Tobias Schulze, Manfred Sengl, Benjamin A. Shoemaker, Kerry Sims, Heinz Singer, Randolph R. Singh, Mark Sumarah, Paul A. Thiessen, Kevin Thomas, Sonia Torres, Xenia Trier, Annemarie P. van Wezel, Roel C. H. Vermeulen, Jelle J. Vlaanderen, Peter C. von der Ohe, Zhanyun Wang, Antony J. Williams, Egon L. Willighagen, David S. Wishart, Jian Zhang, Nikolaos S. Thomaidis, Juliane Hollender, Jaroslav Slobodnik, Emma L. Schymanski
Summary: The NORMAN Suspect List Exchange (NORMAN-SLE) is a global chemical information resource that hosts valuable suspect screening lists for the environmental community. It contains 99 separate lists from over 70 contributors, totaling over 100,000 unique substances. The NORMAN-SLE allows integration with other major chemical resources, fostering the exchange of information and supporting the paradigm shift to a one substance, one assessment approach.
ENVIRONMENTAL SCIENCES EUROPE
(2022)
Article
Substance Abuse
Benjamin J. Tscharke, Jake W. O'Brien, Fahad Ahmed, Lynn Nguyen, Maulik Ghetia, Gary Chan, Phong Thai, Cobus Gerber, Richard Bade, Jochen Mueller, Kevin V. Thomas, Jason White, Wayne Hall
Summary: Wastewater-based epidemiology was used to measure changes in population codeine consumption in Australia after it was rescheduled from an over-the-counter to a prescription-only medicine in 2018. The study found that the average per-capita consumption of codeine decreased by approximately 37% nationally, with significant decreases observed in all states. Areas with less pharmacy access experienced larger decreases in consumption compared to areas with greater pharmacy access. Wastewater analysis can effectively evaluate changes in population pharmaceutical consumption in response to drug scheduling changes.
Article
Chemistry, Analytical
Richard Bade, Geoff Eaglesham, Katja M. Shimko, Jochen Mueller
Summary: The growing NPS market poses challenges for public health officers, law enforcement, and chemists. The development of analytical methods is hindered by the low doses, unknown metabolism, and diverse chemical classes of NPS. This study presents a direct injection method to quantify 32 NPS, demonstrating its validity and identifying several NPS in wastewater samples from Australia.
Article
Radiology, Nuclear Medicine & Medical Imaging
Joshua R. Astley, Alberto M. Biancardi, Paul J. C. Hughes, Helen Marshall, Guilhem J. Collier, Ho-Fung Chan, Laura C. Saunders, Laurie J. Smith, Martin L. Brook, Roger Thompson, Sarah Rowland-Jones, Sarah Skeoch, Stephen M. Bianchi, Matthew Q. Hatton, Najib M. Rahman, Ling-Pei Ho, Chris E. Brightling, Louise V. Wain, Amisha Singapuri, Rachael A. Evans, Alastair J. Moss, Gerry P. McCann, Stefan Neubauer, Betty Raman, Jim M. Wild, Bilal A. Tahir
Summary: A generalizable 3D CNN was developed for lung segmentation in 1H-MRI, demonstrating robustness to pathology, acquisition protocol, vendor, and center.
JOURNAL OF MAGNETIC RESONANCE IMAGING
(2023)
Article
Engineering, Environmental
Richard Bade, Nikolaos Rousis, Sangeet Adhikari, Christine Baduel, Lubertus Bijlsma, Erasmia Bizani, Tim Boogaerts, Daniel A. Burgard, Sara Castiglioni, Andrew Chappell, Adrian Covaci, Erin M. Driver, Fernando Fabriz Sodre, Despo Fatta-Kassinos, Aikaterini Galani, Cobus Gerber, Emma Gracia-Lor, Elisa Gracia-Marin, Rolf U. Halden, Ester Heath, Felix Hernandez, Emma Jaunay, Foon Yin Lai, Heon-Jun Lee, Maria Laimou-Geraniou, Jeong-Eun Oh, Kristin Olafsdottir, Kaitlyn Phung, Marco Pineda Castro, Magda Psichoudaki, Xueting Shao, Noelia Salgueiro-Gonzalez, Rafael Silva Feitosa, Cezar Silvino Gomes, Bikram Subedi, Arndis Sue Ching Love, Nikolaos Thomaidis, Diana Tran, Alexander van Nuijs, Taja Verovsek, Degao Wang, Jason M. White, Viviane Yargeau, Ettore Zuccato, Jochen F. Mueller
Summary: The proliferation of new psychoactive substances (NPS) has made their surveillance complex. This study analyzes data from an international wastewater surveillance program, which collected and analyzed influent wastewater samples from multiple countries. The study finds that NPS are used across different continents and countries, with variations in usage patterns across regions. Wastewater surveillance provides valuable insights into temporal and spatial trends of NPS use.
Article
Environmental Sciences
Nikolaos Rousis, Richard Bade, Ivan Romero-Sanchez, Jochen F. Mueller, Nikolaos S. Thomaidis, Kevin Thomas, Emma Gracia-Lor
Summary: The market for illicit drugs and new psychoactive substances (NPS) has increased significantly and festivals are identified as high-risk environments for substance use. Traditional surveillance methods have limitations, and wastewater-based epidemiology (WBE) proves to be a cost-effective and timely alternative. Utilizing WBE, a study was conducted in a large city in Spain during the New Year period and a summer Festival, identifying high consumption rates of specific NPS and illicit drugs, as well as dynamic changes in their use patterns over a six-month period. The study highlights the importance of WBE in complementing public health information and providing insights into drug use trends at festivals.
ENVIRONMENT INTERNATIONAL
(2023)
Article
Critical Care Medicine
Laura C. Saunders, Guilhem J. Collier, Ho-Fung Chan, Paul J. C. Hughes, Laurie J. Smith, J. G. R. Watson, James E. Meiring, Zoe Gabriel, Thomas Newman, Megan Plowright, Phillip Wade, James A. Eaden, Siby Thomas, Scarlett Strickland, Lotta Gustafsson, Jody Bray, Helen Marshall, David A. Capener, Leanne Armstrong, Jennifer Rodgers, Martin Brook, Alberto M. Biancardi, Madhwesha R. Rao, Graham Norquay, Oliver Rodgers, Ryan Munro, James E. Ball, Neil J. Stewart, Allan Lawrie, R. Gisli Jenkins, James T. Grist, Fergus Gleeson, Rolf F. Schulte, Kevin M. Johnson, Frederick J. Wilson, Anthony Cahn, Andrew J. Swift, Smitha Rajaram, Gary H. Mills, Lisa Watson, Paul J. Collini, Rod Lawson, A. A. Roger Thompson, Jim M. Wild
Summary: This study aimed to investigate whether patients hospitalized with COVID-19 showed long-term improvements in lung function between 6 and 52 weeks following hospitalization, without evidence of architectural distortion on structural imaging. The study found that lung gas transfer remained impaired up to 1 year after hospitalization, while lung ventilation was normal at 52 weeks.
Meeting Abstract
Critical Care Medicine
H. Marshall, L. J. Smith, A. Biancardi, G. J. Collier, H. F. Chan, P. J. C. Hughes, M. L. Brook, J. Astley, R. Munro, S. Rajaram, A. J. Swift, D. Capener, J. Bray, J. Ball, O. Rodgers, D. Jakymelen, I. Smith, B. A. Tahir, M. Rao, G. Norquay, N. D. Weatherley, L. Armstrong, L. Hardaker, T. Fihn-Wikander, R. Hughes, J. M. Wild
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(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)