scholarly journals Lessons from the Past and Charting the Future of Marine Natural Products Drug Discovery and Chemical Biology

2012 ◽  
Vol 19 (1) ◽  
pp. 85-98 ◽  
Author(s):  
William H. Gerwick ◽  
Bradley S. Moore
2020 ◽  
Vol 49 (D1) ◽  
pp. D509-D515
Author(s):  
Chuanyu Lyu ◽  
Tong Chen ◽  
Bo Qiang ◽  
Ningfeng Liu ◽  
Heyu Wang ◽  
...  

Abstract Marine organisms are expected to be an important source of inspiration for drug discovery after terrestrial plants and microorganisms. Despite the remarkable progress in the field of marine natural products (MNPs) chemistry, there are only a few open access databases dedicated to MNPs research. To meet the growing demand for mining and sharing for MNPs-related data resources, we developed CMNPD, a comprehensive marine natural products database based on manually curated data. CMNPD currently contains more than 31 000 chemical entities with various physicochemical and pharmacokinetic properties, standardized biological activity data, systematic taxonomy and geographical distribution of source organisms, and detailed literature citations. It is an integrated platform for structure dereplication (assessment of novelty) of (marine) natural products, discovery of lead compounds, data mining of structure-activity relationships and investigation of chemical ecology. Access is available through a user-friendly web interface at https://www.cmnpd.org. We are committed to providing a free data sharing platform for not only professional MNPs researchers but also the broader scientific community to facilitate drug discovery from the ocean.


2018 ◽  
pp. 399-404
Author(s):  
S. Nassir Ghaemi

Newer and better medications are obtained as part of the drug discovery process, which occurs mainly in the pharmaceutical industry. This process is hampered by excessive attention to marketing demands, as opposed to scientific exploration. It also is impaired by the psychiatric profession’s mistaken ideologies, whether psychoanalytic orthodoxy in the past or DSM beliefs of the present. Wrong clinical phenotypes impair finding new pharmacological mechanisms and targeting them well to the write clinical indications. Perhaps as a consequence, no treatments have been developed in the last few decades, since DSM-III, that are more effective than prior agents. Progress for the future in drug discovery will require not just better neurobiological work, but also a new approach to clinical diagnoses in psychiatry.


RSC Advances ◽  
2020 ◽  
Vol 10 (57) ◽  
pp. 34959-34976
Author(s):  
Enas Reda Abdelaleem ◽  
Mamdouh Nabil Samy ◽  
Samar Yehia Desoukey ◽  
Miaomiao Liu ◽  
Ronald J. Quinn ◽  
...  

Marine organisms have been considered an interesting target for the discovery of different classes of secondary natural products with wide-ranging biological activities.


Author(s):  
Oyere Tanyi Ebob ◽  
Smith B. Babiaka ◽  
Fidele Ntie-Kang

AbstractFor the past 2 years, the coronavirus responsible for the COVID-19 infection has become a world pandemic, ruining the lives and economies of several nations in the world. This has scaled up research on the virus and the resulting infection with the goal of developing new vaccines and therapies. Natural products are known to be a rich source of lead compounds for drug discovery, including against infectious diseases caused by microbes (viruses, bacteria and fungi). In this review article, we conducted a literature survey aimed at identifying natural products with inhibitory concentrations against the coronaviruses or their target proteins, which lie below 10 µM. This led to the identification of 42 compounds belonging to the alkaloid, flavonoid, terpenoid, phenolic, xanthone and saponin classes. The cut off concentration of 10 µM was to limit the study to the most potent chemical entities, which could be developed into therapies against the viral infection to make a contribution towards limiting the spread of the disease.


2019 ◽  
Author(s):  
Paul Kelly ◽  
Fatemeh Hadi-Nezhad ◽  
Dennis Liu ◽  
Travis J. Lawrence ◽  
Roger G. Linington ◽  
...  

AbstractThe development of chemotherapies against eukaryotic pathogens is especially challenging because of both the evolutionary conservation of drug targets between host and parasite, and the evolution of strain-dependent drug resistance. There is a strong need for new nontoxic drugs with broad-spectrum activity against trypanosome parasites such as Leishmania and Trypanosoma. A relatively untested approach is to target macromolecular interactions in parasites rather than small molecular interactions, under the hypothesis that the features specifying macromolecular interactions diverge more rapidly through coevolution. We computed tRNA Class-Informative Features in humans and eight clades of trypanosomes, identifying parasite-specific informative features (including base-pairs and base mis-pairs) that are broadly conserved over approximately 250 million years of trypanosome evolution. Validating these observations, we demonstrated biochemically that tRNA:aminoacyl-tRNA synthetase interactions are a promising target for anti-trypanosomal drug discovery. From a marine natural products extract library, we identified several fractions with inhibitory activity toward Leishmania major alanyl-tRNA synthetase (AlaRS) but no activity against the human homolog. These marine natural products extracts showed cross-reactivity towards Trypanosoma cruzi AlaRS indicating the broad-spectrum potential of our network predictions. These findings support a systems biology model in which combination chemotherapies that target multiple tRNA-synthetase interactions should be comparatively less prone to the emergence of resistance than conventional single drug therapies.Author SummaryTrypanosome parasites pose a significant health risk worldwide. Conventional drug development strategies have proven challenging given the high conservation between humans and pathogens, with off-target toxicity being a common problem. Protein synthesis inhibitors have historically been an attractive target for antimicrobial discovery against bacteria, and more recently for eukaryotic pathogens. Here we propose that exploiting pathogen-specific tRNA-synthetase interactions offers the potential for highly targeted drug discovery. To this end, we improved tRNA gene annotations in trypanosome genomes, identified functionally informative trypanosome-specific tRNA features, and showed that these features are highly conserved over approximately 250 million years of trypanosome evolution. Highlighting the species-specific and broad-spectrum potential of our approach, we identified natural product inhibitors against the parasite translational machinery that have no effect on the homologous human enzyme.


Planta Medica ◽  
2015 ◽  
Vol 81 (11) ◽  
Author(s):  
JR Tormo ◽  
D Oves ◽  
R Lacret ◽  
C Moreno ◽  
M DeLa Cruz ◽  
...  

2019 ◽  
Vol 23 (8) ◽  
pp. 901-919 ◽  
Author(s):  
Yaorui Ma ◽  
Junfei Luo

Amide bonds are amongst the most fundamental groups in organic synthesis, and they are widely found in natural products, pharmaceuticals and material science. Over the past decade, methods for the direct amination of aldehydes have received much attention as they represent atom- and step-economic routes for amide synthesis from readily available starting materials. Herein, the research advances on the direct amination of aldehydes are reviewed and categorized by the types of catalyst system. Detailed reaction scopes and mechanisms will be discussed, as well as the limitations of current procedures and the prospects for the future.


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