Review
Biochemistry & Molecular Biology
Li-Juan Deng, Wei-Qing Deng, Shu-Ran Fan, Min-Feng Chen, Ming Qi, Wen-Yu Lyu, Qi Qi, Amit K. Tiwari, Jia-Xu Chen, Dong-Mei Zhang, Zhe-Sheng Chen
Summary: Abnormal N6-methyladenosine (m6A) modification is closely related to cancer development, and finding targeted anticancer drugs is important. Traditional herbs and computer-synthesized compounds are reasonable sources for these drugs. Artificial intelligence has advantages in discovering m6A-targeting anticancer drugs.
Article
Chemistry, Multidisciplinary
Hong-Quan Xu, Huan Xiao, Jin-Hui Bu, Yan-Feng Hong, Yu-Hong Liu, Zi-Yue Tao, Shu-Fan Ding, Yi-Tong Xia, E. Wu, Zhen Yan, Wei Zhang, Gong-Xing Chen, Feng Zhu, Lin Tao
Summary: The study introduces a comprehensive database for endophytic microorganism natural products (EMNPD), which aims to meet the increasing demand for data mining and sharing in this field. This database provides a wealth of natural product data and links to other databases, facilitating drug discovery and exploration of bioactive substances.
JOURNAL OF CHEMINFORMATICS
(2023)
Review
Pharmacology & Pharmacy
Yihui Song, Xiaoke Yang, Bin Yu
Summary: Drug repurposing is an attractive strategy for finding new indications for existing drugs. Three approved antidepressants have shown potential in clinical trials for cancer treatment. By conducting further medicinal chemistry research, several TCP-based inhibitors of the histone lysine specific demethylase 1 enzyme have been discovered, showing promise for cancer treatment. Repurposing antidepressants could be a promising strategy for cancer treatment.
DRUG DISCOVERY TODAY
(2022)
Article
Biochemistry & Molecular Biology
Firdoos Ahmad Sofi, Nahida Tabassum
Summary: Natural products are crucial for discovering and developing new anti-cancer drugs, with plant-derived drugs accounting for about 60% of the total. Anti-cancer leads have been found in plants, animals, marine organisms, and microorganisms throughout history. By modifying the parent leads, new anti-cancer agents with improved efficacy and fewer side effects can be created. Various techniques such as chemo-informatics, bioinformatics, high-throughput screening, and combinatorial synthesis can be utilized to identify new natural product leads.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Chemistry, Medicinal
Junjie Li, Rui Zhao, Peiran Miao, Fengfeng Xu, Jiahao Chen, Xiaoying Jiang, Zi Hui, Liwei Wang, Renren Bai
Summary: This review provides a comprehensive overview of the diverse anti-inflammatory activities of flavonoids and elucidates the underlying pathways in mediating inflammation. It includes a systematic classification and detailed statistical analysis of flavonoids, related anti-inflammatory targets, and in vitro and in vivo test models. The review aims to provide practical information and potential leads for researchers engaged in natural products and anti-inflammatory drug discovery.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Vivek P. P. Chavda, Yavuz Nuri Ertas, Vinayak Walhekar, Dharti Modh, Avani Doshi, Nirav Shah, Krishna Anand, Mahesh Chhabria
Summary: Investigations into natural chemical compounds for their programmed necrosis potential have led to the emergence of multi-target drugs and new drug discovery methods like fragment-based drug discovery for natural anticancer agents.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Jia Fu, Wei Qin, Lu-Qi Cao, Zhe-Sheng Chen, Hui-Ling Cao
Summary: This review summarizes the applications and immobilization methods of receptor chromatography, which is widely used for high-throughput separation and accurate drug screening. The review focuses on screening active compounds in natural products, as well as the design and application of receptor chromatography in drug-receptor interactions.
DRUG DISCOVERY TODAY
(2023)
Review
Biochemistry & Molecular Biology
Yuin Chang, Keng Yoon Yeong
Summary: Since the discovery of the regulatory roles of sirtuins in various pathological processes, there has been a growing interest in researching sirtuins, particularly in the development of modulators. Natural modulators have therapeutic potential in treating various diseases, and this review provides insights into their molecular mechanisms, therapeutic benefits, as well as the challenges and future prospects in drug discovery.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Gulshan Kumar, Chinmay Das, Ayan Acharya, Subhasmita Bhal, Mayank Joshi, Chanakya Nath Kundu, Angshuman Roy Choudhury, Sankar K. Guchhait
Summary: A Nature-to-new strategy was employed to investigate analogs of natural aurones, using iterative scaffold-hopping. A method based on organocatalyzed umpolung chemistry was established for the synthesis of (Z)-2-Arylideneimidazo [1,2-a]pyridinones and (Z)-2-Arylidenebenzo[d]imidazo[2,1-b]thiazol-3-ones. Biophysical experiments demonstrated the significant biological properties of these analogs, particularly their anticancer activities.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Yijia Zhao, Huafeng Pan, Wei Liu, E. Liu, Yaobin Pang, Hongjin Gao, Qingying He, Wenhao Liao, Yejing Yao, Jinhao Zeng, Jing Guo
Summary: This study reviewed the anticancer activity and underlying mechanism of menthol, highlighting its safety profile and multiple pathways of action. Due to its excellent anticancer activity, further research is needed to develop menthol as a novel anticancer agent.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Nutrition & Dietetics
Ahyeon Kim, Jiwon Ha, Jeongeun Kim, Yongmin Cho, Jimyung Ahn, Chunhoo Cheon, Sung-Hoon Kim, Seong-Gyu Ko, Bonglee Kim
Summary: Natural products have potential effects in treating pancreatic cancer, particularly through inducing cell apoptosis. Plant extracts are the main focus in the research, while some natural products exhibit multifunctional properties.
Article
Chemistry, Multidisciplinary
Sourav Pakrashy, Prakash K. Mandal, Surya Kanta Dey, Sujata Maiti Choudhury, Fatmah Ali Alasmary, Amani Salem Almalki, Md Ataul Islam, Malay Dolai
Summary: Scaffold architecture plays an important role in biotechnology and drug discovery research, aiding in the search for potential drug candidates and generating new compound structures. This study successfully developed a pharmacophore-guided drug candidate for SARS-CoV-2 or Covid 19 using natural product hopping and molecular modelling techniques.
Review
Biochemistry & Molecular Biology
Zhihong Xu, Barrett Eichler, Eytan A. A. Klausner, Jetty Duffy-Matzner, Weifan Zheng
Summary: Natural products and their derivatives have shown to be effective drug candidates against various diseases. This paper reviews potent anticancer, anti-HIV, antibacterial, and antimalarial drugs or lead compounds discovered mainly from 2016 to 2022, as well as computer-assisted techniques used in designing new structures based on available natural products.
Review
Pharmacology & Pharmacy
Dongqin Xia, Wenjie Li, Ce Tang, Juan Jiang
Summary: Cancer is increasing in developing countries with unsatisfactory outcomes from traditional cancer treatments. Traditional Chinese medicine (TCM) components, such as Astragaloside IV (AS-IV), have shown significant anticancer activities. AS-IV has various effects, including modulation of enzyme activities, cell cycle arrest, apoptosis and autophagy induction, and suppression of cancer progression. This article reviews the bioavailability, anticancer activity, and mechanism of AS-IV and provides suggestions for further research.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Wei Wang, Shan Zhang, Jianhua Wang, Furan Wu, Tao Wang, Gong Xu
Summary: A series of potential novel fungicides were designed and synthesized, with two compounds showing significant antifungal activities against various fungi. These compounds could be promising candidates for the development of new fungicides in crop protection.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Patrick Maeder, Ruben Bartholomaeus, Simon Nicolussi, Alice Baumann, Melanie Weis, Andrea Chicca, Mark Rau, Ana Catarina Simao, Juerg Gertsch, Karl-Heinz Altmann
Summary: WOBE437 is a highly potent inhibitor of endocannabinoid reuptake, and its analogues synthesized in this study showed similarly potent effects on anandamide uptake. Some of the compounds demonstrated high selectivity and significant activity differences when methoxy substituents in the head group were replaced. These compounds could serve as interesting starting points for developing potent endocannabinoid uptake inhibitors with improved drug-like properties.
Article
Chemistry, Multidisciplinary
Christian Paul Bold, Melanie Gut, Jasmine Schurmann, Daniel Lucena-Agell, Jurg Gertsch, Jose Fernando Diaz, Karl-Heinz Altmann
Summary: The study describes the convergent synthesis of analogues of the marine macrolide (-)-zampanolide, incorporating an embedded N-substituted morpholine moiety. Among the three investigated morpholino-zampanolides, the N-acetyl and N-benzoyl derivatives both showed nanomolar antiproliferative activity, while the N-tosyl derivative had significantly reduced activity.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Neurosciences
Lena-Louise Schuele, Sandra Glasmacher, Juerg Gertsch, Marie Denise Roggan, Janis-Lisa Transfeld, Laura Bindila, Beat Lutz, Carl-Christian Kolbe, Andras Bilkei-Gorzo, Andreas Zimmer, Este Leidmaa
Summary: Genetic deletion of CB1 receptors or DAGLa enzyme leads to significant behavioral changes related to depression in animal models. Astrocytes in the brain play a key regulatory role in affective behaviors by contributing to lipid metabolism through the DAGLa pathway.
Article
Chemistry, Medicinal
Carlotta Granchi, Giulia Bononi, Rebecca Ferrisi, Eleonora Gori, Giulia Mantini, Sandra Glasmacher, Giulio Poli, Stefano Palazzolo, Isabella Caligiuri, Flavio Rizzolio, Vincenzo Canzonieri, Tiziana Perin, Juerg Gertsch, Andrea Sodi, Elisa Giovannetti, Marco Macchia, Filippo Minutolo, Tiziano Tuccinardi, Andrea Chicca
Summary: The manuscript expands and optimizes the class of benzoylpiperidine-based MAGL inhibitors, which selectively inhibit MAGL against other components of the endocannabinoid system. Experimental results demonstrate the potential use of these compounds as anticancer agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Food Science & Technology
Simon Vlad Luca, Mirjana Minceva, Jurg Gertsch, Krystyna Skalicka-Wozniak
Summary: This study used LC-HRMS/MS technology to investigate the piperamides in various Piper plants and their modulation of the endocannabinoid system. The results showed that P. nigrum and P. longum have similar piperamide profiles, while other Piper spices may have different metabolite patterns.
FOOD RESEARCH INTERNATIONAL
(2021)
Article
Anesthesiology
Thomas Andrieu, Andrea Chicca, Daniele Pellegata, Nick A. Bersinger, Sara Imboden, Konstantinos Nirgianakis, Juerg Gertsch, Michael D. Mueller
Summary: This case-control study found that levels of endocannabinoids (eCBs) are significantly influenced by both noncyclic and cyclic abdominal pain, suggesting a potential role of the eCB system in endometriosis-associated pain.
Article
Oncology
Thomas Gruber, Steve Robatel, Mirela Kremenovic, Lukas Bariswyl, Jurg Gertsch, Mirjam Schenk
Summary: The study highlights the critical role of CB2R in regulating tumor immunity in melanoma, with high CB2R gene expression associated with improved overall survival. Mouse models and in-depth analysis of tumor-infiltrating lymphocytes suggest that CB2R deficiency may lead to an immunosuppressive microenvironment by affecting B cell differentiation. This insight could potentially inform the development of novel CB2R-targeted cancer therapies.
Article
Cell Biology
Renhong Yan, Yaning Li, Jennifer Mueller, Yuanyuan Zhang, Simon Singer, Lu Xia, Xinyue Zhong, Jurg Gertsch, Karl-Heinz Altmann, Qiang Zhou
Summary: LAT1 is a representative light chain protein of heteromeric amino acid transporters, overexpressed in many types of tumors and considered a drug target for cancer treatment. The cryo-EM structures of LAT1-4F2hc complexes reveal an outward-facing occluded conformation and a different inhibition mechanism, providing important insights for future drug design.
Article
Multidisciplinary Sciences
Andrea Salm, Sandhya R. Krishnan, Marta Collu, Ombeline Danton, Matthias Hamburger, Marco Leonti, Giovanna Almanza, Jurg Gertsch
Summary: This study conducted a cross-sectional ethnopharmacological field study in Bolivia, discovering potential antichagasic botanical drugs and identifying hydroxyanthraquinone as a potential lead scaffold for anti-Trypanosoma cruzi drugs. The research suggests that phylogenetic hotspots in the plant kingdom may be a valuable resource for drug discovery based on ethnopharmacological hypotheses.
Article
Multidisciplinary Sciences
Joanna Kowalczyk, Barbara Budzynska, Lukasz Kurach, Daniele Pellegata, Nesrine S. El Sayed, Jurg Gertsch, Krystyna Skalicka-Wozniak
Summary: Scoparone, a compound found in traditional Chinese medicine and Genepi liquor, has been found to have potent central effects in mice, which may have toxicopharmacological implications for humans.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Medicinal
Giulia Bononi, Miriana Di Stefano, Giulio Poli, Gabriella Ortore, Philip Meier, Francesca Masetto, Isabella Caligiuri, Flavio Rizzolio, Marco Macchia, Andrea Chicca, Amir Avan, Elisa Giovannetti, Chiara Vagaggini, Annalaura Brai, Elena Dreassi, Massimo Valoti, Filippo Minutolo, Carlotta Granchi, Juerg Gertsch, Tiziano Tuccinardi
Summary: The study reveals the potential of benzylpiperidine-based MAGL inhibitors in pancreatic cancer treatment. Inhibition of MAGL can reduce cell migration and promote apoptosis, synergizing with chemotherapy drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Liad Hinden, Majdoleen Ahmad, Sharleen Hamad, Alina Nemirovski, Gergo Szanda, Sandra Glasmacher, Aviram Kogot-Levin, Rinat Abramovitch, Bernard Thorens, Jurg Gertsch, Gil Leibowitz, Joseph Tam
Summary: This study reveals that the activation of cannabinoid-1 receptor (CB1R) and mammalian target of rapamycin complex 1 (mTORC1) in renal proximal tubular cells (RPTCs) is involved in the development of diabetic kidney disease (DKD). Stimulation of endocannabinoid/CB1R by hyperglycemia increases mTORC1 activity and promotes the transcription of facilitative glucose transporter 2 (GLUT2), leading to DKD in mice. Conversely, CB1R maintains the normal activity of mTORC1 by preventing amino acid uptake during normoglycemia. This finding highlights the importance of the CB1/mTORC1/GLUT2 signaling axis in regulating nutrient homeostasis in healthy and diseased kidneys.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Julien Graff, Jennifer Mueller, Anna Sadurni, Matthias Rubin, Ines Andre Canivete Cuissa, Claudia Keller, Marco Hartmann, Simon Singer, Jurg Gertsch, Karl-Heinz Altmann
Summary: A series of derivatives of the substrate amino acid l-tryptophan have been investigated for inhibition of the L-type amino acid transporter LAT1. The 5-substituted derivative showed the highest potency, while the replacement of the carboxy group led to a complete loss in potency. Increasing the steric bulk at the 5-position did not improve the inhibitory activity. None of these derivatives were found to be substrates for LAT1-mediated transport.
Article
Chemistry, Multidisciplinary
Jean-Marc Jeckelmann, Jonas Zaugg, Veronika Morozova, Jennifer Mueller, Satish Kantipudi, Mariana Schroeder, Julien Graff, Christiane Albrecht, Karl-Heinz Altmann, Jurg Gertsch, Dimitrios Fotiadis
Summary: Amino acids are vital for living cells and their transporters play crucial roles in transferring amino acids and studying human diseases.
Article
Chemistry, Multidisciplinary
Thais Gazzi, Benjamin Brennecke, Kenneth Atz, Claudia Korn, David Sykes, Gabriel Forn-Cuni, Patrick Pfaff, Roman C. Sarott, Matthias Westphal, Yelena Mostinski, Leonard Mach, Malgorzata Wasinska-Kalwa, Marie Weise, Bradley L. Hoare, Tamara Miljus, Maira Mexi, Nicolas Roth, Eline J. Koers, Wolfgang Guba, Andre Alker, Arne C. Rufer, Eric A. Kusznir, Sylwia Huber, Catarina Raposo, Elisabeth A. Zirwes, Anja Osterwald, Anto Pavlovic, Svenja Moes, Jennifer Beck, Matthias Nettekoven, Irene Benito-Cuesta, Teresa Grande, Faye Drawnel, Gabriella Widmer, Daniela Holzer, Tom van der Wel, Harpreet Mandhair, Michael Honer, Jurgen Fingerle, Joerg Scheffel, Johannes Broichhagen, Klaus Gawrisch, Julian Romero, Cecilia J. Hillard, Zoltan V. Varga, Mario van der Stelt, Pal Pacher, Jurg Gertsch, Christoph Ullmer, Peter J. McCormick, Sergio Oddi, Herman P. Spaink, Mauro Maccarrone, Dmitry B. Veprintsev, Erick M. Carreira, Uwe Grether, Marc Nazare
Summary: This study reports the development of a novel fluorescent CB2R agonist probe that can detect CB2R in living cells and zebrafish larvae. These findings contribute to the clinical translatability of CB2R-based drugs.