Review
Chemistry, Medicinal
Mohammad Bagherniya, Hamed Khedmatgozar, Omid Fakheran, Suowen Xu, Thomas P. Johnston, Amirhossein Sahebkar
Summary: The NLRP3 inflammasome is a multiprotein complex that is activated by a wide range of danger signals resulting from metabolic dysregulation. Nutraceuticals and medicinal plants have antiinflammatory properties and can be used as complementary therapy in chronic diseases related to inflammation by inhibiting NLRP3 inflammasome activation. Herb-based medicine has shown protective effects against NLRP3 inflammasome activation.
PHYTOTHERAPY RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Maria Sorokina, Peter Merseburger, Kohulan Rajan, Mehmet Aziz Yirik, Christoph Steinbeck
Summary: Natural products (NPs) are bioactive small molecules produced by living organisms, sparking global interest in NP research. Despite the existence of multiple NP databases, there is currently no resource that aggregates all known NPs in one place, which would greatly simplify research.
JOURNAL OF CHEMINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Oscar Salvador Barrera-Vazquez, Juan Carlos Gomez-Verjan, Gil Alfonso Magos-Guerrero
Summary: Cellular senescence is a condition that involves significant changes in gene expression and cell proliferation arrest. Recent studies have suggested that pharmacological elimination of senescent cells can delay, prevent, and improve adverse outcomes related to age. Through the use of chemoinformatic tools in natural product chemical databases, new senolytic compounds candidates were discovered.
Article
Chemistry, Multidisciplinary
R. P. Vivek-Ananth, Karthikeyan Mohanraj, Ajaya Kumar Sahoo, Areejit Samal
Summary: IMPPAT 2.0 is an enhanced and expanded database that compiles manually curated information on 4010 Indian medicinal plants, 17,967 phytochemicals, and 1095 therapeutic uses. It also provides a nonredundant in silico stereo-aware library of 17,967 phytochemicals from Indian medicinal plants.
Article
Plant Sciences
Menghan Zhang, Zhaoyong Shi, Shan Zhang, Jiakai Gao
Summary: This study establishes a database on the mycorrhizal traits of medicinal plants, providing information on mycorrhizal types and status. Results show that the majority of medicinal plants have an obligate symbiotic relationship with mycorrhizal fungi, with the most common type being AM. This database serves as a valuable resource for identifying mycorrhizal information of medicinal plants and enriching the theory of mycorrhizal traits, making it highly significant for the production and management of medicinal plants.
FRONTIERS IN PLANT SCIENCE
(2022)
Review
Pharmacology & Pharmacy
Dongpeng Wang, Xian-He Wang, Xiongjie Yu, Fengjun Cao, Xiaojun Cai, Ping Chen, Minglun Li, Yibin Feng, Hongliang Li, Xuanbin Wang
Summary: Anthraquinones are bioactive natural products with various pharmacological effects. They are mainly absorbed in the intestines and distributed in blood flow-rich tissues and organs. Transformation into another anthraquinone may increase the blood concentration of the latter, leading to an enhanced pharmacological and/or toxicological effect.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Omid Yazarlu, Mehrdad Iranshahi, Hamid Reza Khayat Kashani, Sara Reshadat, Solomon Habtemariam, Milad Iranshahy, Maede Hasanpour
Summary: Herbal medicines play a significant role in wound healing by stimulating various mechanisms such as reepithelialization, angiogenesis, and collagen fiber deposition. Some herbal medicines also exhibit antioxidant and anti-inflammatory properties by inhibiting specific protein expression. Compared to conventional medicines, herbal medicine and natural products offer advantages in wound healing due to their diverse mechanisms of action, antibacterial activity, and long-term safety in usage.
PHARMACOLOGICAL RESEARCH
(2021)
Review
Chemistry, Medicinal
Jose Alixandre de Sousa Luis, Renata Priscila Costa Barros, Natalia Ferreira de Sousa, Eugene Muratov, Luciana Scotti, Marcus Tullius Scotti
Summary: This paper introduces the main databases of natural products and virtual screening strategies for identifying potential drug molecules. Through a search in the Web of Science database, 230 articles were evaluated, with 104 selected for review based on research criteria, showing a variety of potential drug candidates for different diseases.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Faris Alrumaihi
Summary: The study identified three small natural molecules with strong binding potential for the allosteric pocket of the CC chemokine receptor 7 through virtual screening. Molecular dynamics simulations showed these compounds forming strong chemical bonds and experiencing conformation changes, supported by two types of binding energy analyses. The compounds also passed various safety parameters and are considered promising anti-cancer candidates for experimental testing.
Review
Pharmacology & Pharmacy
Fei Tang, Hong-Ling Yan, Li-Xia Wang, Jin-Feng Xu, Cheng Peng, Hui Ao, Yu-Zhu Tan
Summary: This study highlights the importance of traditional Chinese medicine and natural products in the prevention and treatment of cardiovascular and cerebrovascular diseases, providing comprehensive references on hypertension and CCVDs, and emphasizing the different mechanisms of action of traditional Chinese medicine and natural products.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Leticia Tiburcio Ferreira, Joyce V. B. Borba, Jose Teofilo Moreira-Filho, Aline Rimoldi, Carolina Horta Andrade, Fabio Trindade Maranhao Costa
Summary: Malaria remains a public health burden in tropical and subtropical areas, with drug-resistant Plasmodium strains driving the exploration of novel antimalarial compounds. Through virtual screening, promising natural compound-based antimalarial molecules can be identified for further development.
Review
Plant Sciences
Samuel Scott, Edgar B. Cahoon, Lucas Busta
Summary: Plants have the ability to produce lineage-specific natural products from their core metabolic pathways. However, little attention has been given to natural products derived from fatty acids. Recent studies have shown that plants can produce structurally diverse compounds from fatty acids, some of which have unique structural features and novel functionalities. This review aims to summarize the current knowledge of fatty acid-derived natural products and their biosynthesis, and suggest future research priorities.
Article
Biochemistry & Molecular Biology
Kathleen Gallo, Emanuel Kemmler, Andrean Goede, Finnja Becker, Mathias Dunkel, Robert Preissner, Priyanka Banerjee
Summary: Natural products have been used for thousands of years as healing agents and continue to be a major source of potential therapeutic preparations. They have played a key role in modern drug discovery and efforts have been made to discover natural low-calorie sweeteners. The SuperNatural 3.0 database provides a valuable resource for natural compounds and derivatives, including information on their structures, physicochemical properties, pathways, and toxicities.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biology
Kikrusenuo Kiewhuo, Dipshikha Gogoi, Hridoy Jyoti Mahanta, Ravindra K. Rawal, Debabrata Das, G. Narahari Sastry
Summary: The study aims to develop a comprehensive resource of medicinal plants and conduct quantitative analysis of their phytochemicals for enhanced understanding of therapeutic indications and contribution to drug discovery and development. The database contains extensive information on medicinal plants and phytochemicals and can be utilized by various research groups, as well as contribute to the economic growth of the pharmaceutical industry.
COMPUTATIONAL BIOLOGY AND CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Luis D. Gonzalez-Morales, Adriana Moreno-Rodriguez, Lenci K. Vazquez-Jimenez, Timoteo Delgado-Maldonado, Alfredo Juarez-Saldivar, Eyra Ortiz-Perez, Alma D. Paz-Gonzalez, Edgar E. Lara-Ramirez, Lilian Yepez-Mulia, Patricia Meza, Gildardo Rivera
Summary: Cutaneous leishmaniasis (CL) is a global public health problem without available vaccines and with limited effective treatments. This study performed virtual screening of natural products against Leishmania mexicana using molecular docking, and selected four compounds with promising leishmanicidal activity. The ADME-Tox analysis suggested favorable properties for these compounds, and one of them, S-8, exhibited higher activity than the reference drug glucantime.
Article
Biochemistry & Molecular Biology
Hany S. Ibrahim, Mohamed Abdelsalam, Yanira Zeyn, Matthes Zessin, Al-Hassan M. Mustafa, Marten A. Fischer, Patrik Zeyen, Ping Sun, Emre F. Buelbuel, Anita Vecchio, Frank Erdmann, Matthias Schmidt, Dina Robaa, Cyril Barinka, Christophe Romier, Mike Schutkowski, Oliver H. Kraemer, Wolfgang Sippl
Summary: In this study, a novel series of selective Class I HDAC inhibitors were synthesized and tested in vitro and in vivo. The most potent compound showed strong inhibitory effects and potential for treating various types of blood cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Ehab Ghazy, Mohamed Abdelsalam, Dina Robaa, Raymond J. Pierce, Wolfgang Sippl
Summary: This review focuses on the recent development of inhibitors for schistosome histone deacetylases, particularly inhibitors of Schistosoma mansoni histone deacetylase 8, which have shown promise for the treatment of schistosomiasis.
Article
Biochemistry & Molecular Biology
Matthes Zessin, Marat Meleshin, Lucas Praetorius, Wolfgang Sippl, Cyril Barinka, Mike Schutkowski
Summary: This study systematically analyzed the acyl-specificity of human zinc-dependent HDAC and sirtuin isoforms. The results showed that HDAC3 has a much higher delactoylase activity compared to SIRT2, which was previously believed to be the major in vivo delactoylase. Additionally, HDAC6 and HDAC8 were found to have high depyruvoylase activity.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Denis Mteremko, Daniel M. Shadrack, Fidele Ntie-Kang, Jaffu Chilongola, Musa Chacha
Summary: 5-fluorouracil and analogs are commonly used in chemotherapy for solid tumors, but resistance and toxicity are common. Repurposing FDA drugs targeting human thymidylate synthase identified several drugs with potential for further development in cancer treatment. The study prioritized four FDA drugs (Erismodegib, Irinotecan, Conivaptan, and Ergotamine) for validation. The role of water in drug interactions and its contribution to binding energy was also explored.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Narges Cheshmazar, Salar Hemmati, Maryam Hamzeh-Mivehroud, Babak Sokouti, Matthes Zessin, Mike Schutkowski, Wolfgang Sippl, Hojjatollah Nozad Charoudeh, Siavoush Dastmalchi
Summary: Histone deacetylases (HDACs), which are overexpressed in cancer, have shown promising results in cancer therapy when inhibited. This study used computational drug design to generate and filter potential HDAC inhibitors based on template structures and a diverse fragment library. Two new structures (3a and 3b) were proposed for synthesis and evaluation, and the compounds showed inhibition on HDAC isoforms.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemistry & Molecular Biology
Emre F. Bulbul, Jelena Melesina, Hany S. Ibrahim, Mohamed Abdelsalam, Anita Vecchio, Dina Robaa, Matthes Zessin, Mike Schutkowski, Wolfgang Sippl
Summary: In this study, a computational approach was used to predict the selectivity of inhibitors targeting HDAC1, HDAC2, and HDAC3. The developed binding free-energy models showed significant correlation between binding free energy and in vitro inhibitory activities, and successfully predicted the efficacy of newly designed inhibitors.
Article
Biochemistry & Molecular Biology
Diana Kalbas, Marat Meleshin, Sandra Liebscher, Matthes Zessin, Jelena Melesina, Cordelia Schiene-Fischer, Emre Fatih Bu''lbu''l, Frank Bordusa, Wolfgang Sippl, Mike Schutkowski
Summary: Sirtuins are protein deacylases involved in regulating metabolism, stress responses, and aging-related diseases. In this study, we synthesized and characterized 3-aryl-mercaptobutyrylated peptide derivatives as effective and selective Sirtuin 2 inhibitors. Our findings suggest that these inhibitors bind to the selectivity pocket of Sirtuin 2, inducing a rearrangement of the active site. Interestingly, 3-aryl-mercapto-nonalyl or palmitoyl derivatives exhibited a different binding mode, blocking both the hydrophobic channel and the nicotinamide pocket.
Article
Plant Sciences
Rajeev K. Singla, Ronita De, Thomas Efferth, Bruno Mezzetti, Md Sahab Uddin, Sanusi, Fidele Ntie-Kang, Dongdong Wang, Fabien Schultz, Kiran R. Kharat, Hari Prasad Devkota, Maurizio Battino, Daniel Sur, Ronan Lordan, Sourav S. Patnaik, Christos Tsagkaris, Chandragiri Siva Sai, Surya Kant Tripathi, Mihnea-Alexandru Gaman, Mosa E. O. Ahmed, Elena Gonzalez-Burgos, Smith B. Babiaka, Shravan Kumar Paswan, Joy Ifunanya Odimegwu, Faizan Akram, Jesus Simal-Gandara, Magali S. Urquiza, Aleksei Tikhonov, Himel Mondal, Shailja Singla, Sara Di Lonardo, Eoghan J. Mulholland, Merisa Cenanovic, Abdulkadir Yusif Maigoro, Francesca Giampieri, Soojin Lee, Nikolay T. Tzvetkov, Anna Maria Louka, Pritt Verma, Hitesh Chopra, Scarlett Perez Olea, Johra Khan, Jose M. Alvarez Suarez, Xiaonan Zheng, Michal Tomczyk, Manoj Kumar Sabnani, Christhian Delfino Villanueva Medina, Garba M. Khalid, Hemanth Kumar Boyina, Milen Georgiev, Claudiu T. Supuran, Eduardo Sobarzo-Sanchez, Tai-Ping Fan, Valeria Pittala, Antoni Sureda, Nady Braidy, Gian Luigi Russo, Rosa Anna Vacca, Maciej Banach, Gerard Lizard, Amira Zarrouk, Sonia Hammami, Ilkay Erdogan Orhan, Bharat B. Aggarwal, George Perry, Mark J. S. Miller, Michael Heinrich, Anupam Bishayee, Anake Kijjoa, Nicolas Arkells, David Bredt, Michael Wink, Bernd L. Fiebich, Gangarapu Kiran, Andy Wai Kan Yeung, Girish Kumar Gupta, Antonello Santini, Massimo Lucarini, Alessandra Durazzo, Amr El-Demerdash, Albena T. Dinkova-Kostova, Alejandro Cifuentes, Eliana B. Souto, Muhammad Asim Masoom Zubair, Pravin Badhe, Javier Echeverria, Jaroslaw Olav Horbanczuk, Olaf K. Horbanczuk, Helen Sheridan, Sadeeq Muhammad Sheshe, Anna Maria Witkowska, Ibrahim M. Abu-Reidah, Muhammad Riaz, Hammad Ullah, Akolade R. Oladipupo, Victor Lopez, Neeraj Kumar Sethiya, Bhupal Govinda Shrestha, Palaniyandi Ravanan, Subash Chandra Gupta, Qushmua E. Alzahrani, Preethidan Dama Sreedhar, Jianbo Xiao, Mohammad Amin Moosavi, Parasuraman Aiya Subramani, Amit Kumar Singh, Ananda Kumar Chettupalli, Jayanta Kumar Patra, Gopal Singh, Tomasz M. Karpinski, Fuad Al-Rimawi, Rambod Abiri, Atallah F. Ahmed, Davide Barreca, Sharad Vats, Said Amrani, Carmela Fimognari, Andrei Mocan, Lucian Hritcu, Prabhakar Semwal, Md Shiblur Rahaman, Mila Emerald, Akinleye Stephen Akinrinde, Abhilasha Singh, Ashima Joshi, Tanuj Joshi, Shafaat Yar Khan, Gareeballah Osman Adam Balla, Aiping Lu, Sandeep Ramchandra Pai, Imen Ghzaiel, Niyazi Acar, Nour Eddine Es-Safi, Gokhan Zengin, Azazahemad A. Kureshi, Arvind Kumar Sharma, Bikash Baral, Neeraj Rani, Philippe Jeandet, Monica Gulati, Bhupinder Kapoor, Yugal Kishore Mohanta, Zahra Emam-Djomeh, Raphael Onuku, Jennifer R. Depew, Omar M. Atrooz, Bey Hing Goh, Jose Carlos Andrade, Bikramjit Konwar, V. J. Shine, Joao Miguel Lousa Dias Ferreira, Jamil Ahmad, Vivek K. Chaturvedi, Krystyna Skalicka-Wozniak, Rohit Sharma, Rupesh K. Gautam, Sebastian Granica, Salvatore Parisi, Rishabh Kumar, Atanas G. Atanasov, Bairong Shen
Summary: The development of digital technologies and open innovation approaches has enabled the creation of virtual organizations and enterprises. The International Natural Product Sciences Taskforce (INPST) is an open innovation platform that brings together individuals and organizations interested in natural product scientific research. This study presents an overview of INPST activities and showcases the use of Twitter as a powerful networking tool, demonstrated through the 2021 INPST Twitter Networking Event.
Editorial Material
Biochemistry & Molecular Biology
Wolfgang Sippl
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Mohamed Abdelsalam, Mariia Zmyslia, Karin Schmidtkunz, Anita Vecchio, Sebastian Hilscher, Hany S. Ibrahim, Mike Schutkowski, Manfred Jung, Claudia Jessen-Trefzer, Wolfgang Sippl
Summary: In this study, a series of prodrugs for class I histone deacetylases (HDACs) were designed and synthesized using known selective HDAC inhibitors. Compound 6 showed the most potent inhibitory activity against nitroreductase (NTR)-transfected leukemic cells.
ARCHIV DER PHARMAZIE
(2023)
Article
Oncology
Ramy Ashry, Al-Hassan M. Mustafa, Kristin Hausmann, Michael Linnebacher, Susanne Strand, Wolfgang Sippl, Matthias Wirth, Oliver H. Kraemer
Summary: Tumors in the pancreas and colon are still a clinical challenge. Different gene expression profiles between cancer cells and normal cells can be targeted by drugs that modulate protein acetylation. KH16 is a novel compound that induces hyperacetylation, leading to cell death in tumor cells while sparing normal cells. It shows superior efficacy compared to clinically established drugs. Further studies can focus on KH16 and similar compounds for cancer therapy.
Article
Chemistry, Medicinal
Emre F. F. Buelbuel, Dina Robaa, Ping Sun, Fereshteh Mahmoudi, Jelena Melesina, Matthes Zessin, Mike Schutkowski, Wolfgang Sippl
Summary: This study analyzed different ligand-based and structure-based drug design techniques to predict the binding mode and inhibitory activity of recently developed alkylhydrazide HDAC inhibitors. Alkylhydrazides have shown promising effects in various cancer cell lines. The created models, including pharmacophore models and atom-based quantitative structure-activity relationship (QSAR) models, explain in vitro data well and were used to develop novel HDAC3 inhibitors.
Article
Biology
Fady Baselious, Dina Robaa, Wolfgang Sippl
Summary: In this study, we optimized the HDAC11 AlphaFold model by adding the catalytic zinc ion and successfully generated stable complexes for docking of selective inhibitors. The most reasonable pose was selected based on structural comparison, and the model explained the binding behavior of known HDAC11 inhibitors.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Review
Chemistry, Multidisciplinary
Conrad V. Simoben, Smith B. Babiaka, Aurelien F. A. Moumbock, Cyril T. Namba-Nzanguim, Donatus Bekindaka Eni, Jose L. Medina-Franco, Stefan Guenther, Fidele Ntie-Kang, Wolfgang Sippl
Summary: The use of traditional medicine has a long history and is still relied upon by many, especially in developing or underprivileged communities. In silico-based methods have played a crucial role in drug discovery, particularly in identifying natural product-based candidates. However, there are challenges in identifying and proposing novel natural product-based hits.
