Marine Biodiscovery: Lead Discovery

Background: Buyang Huanwu Tang (BYHWT) and relevant Traditional Chinese medicine (TCM) has its unique advantages in the treatment of cerebral ischemia. However, its pharmacological mechanism have not been fully explained. Objective: Base on the multi-component, also the entire disease network targets, the present study set out to identify major bioactive ingredients, key disease targets, and pathways of BYHWT against cerebral ischemia disease by systematic pharmacological methodology. Methods: Both the bioactive compounds from the BYHWT and the positive drugs against cerebral ischemia were fully investigated. The binding targets of the positive drugs were then obtained. A virtual screening protocol was then used to highlight the compound-target interaction. And network was constructed to visual the compound-target binding effect after docking analysis. Moreover，the targets enrichment analysis for biological processes and pathways were revealed to further explore the function of bio-targets protein gene and its role in the signal pathway. Results: A total of 382 active ingredients of the BYHWT and 23 candidate disease targets were identified. Virtual screening results indicated that multiple bioactive compounds targeted multiple proteins. Each compounds act on one or more targets. The mechanisms were linked to 20 signaling pathways, and the key mechanism was related to serotonergic synapse, calcium signaling pathway and camp signaling pathways. Conclusion: The present study explored the bioactive ingredients and mechanisms of BYHWT against cerebral ischemia by systematic pharmacological methodology. the novel methodology would provide a reference for the lead discovery of precursors, disease mechanism and material base for TCM.

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Application of Cryo-Electron Microscopy on Drug Discovery

Microscopy and Microanalysis ◽

10.1017/s143192762101120x ◽

2021 ◽

Vol 27 (S1) ◽

pp. 3250-3250

Author(s):

Viswanath Vittaladevaram ◽

Kranthi Kuruti

Keyword(s):

Electron Microscopy ◽

Protein Complexes ◽

Lead Discovery ◽

Biologically Relevant ◽

Biological Targets ◽

3 Dimensional ◽

Drug Molecules ◽

Cryo Electron Microscopy ◽

Therapeutic Molecules ◽

Novel Drug

AbstractThe key aspect for development of novel drug molecules is to perform structural determination of target molecule associated with its ligand. One such tool that provides insights towards structure of molecule is Cryo-electron microscopy which covers biological targets that are intractable. Examination of proteins can be carried out in native state, as the samples are frozen at -175 degree Celsius i.e. cryogenic temperatures. In addition to this, there were no limits for molecular and functional structures of proteins that can be imagined in 3-dimensional form. This includes ligands which unravel mechanisms that are biologically relevant. This will enable to better understand the mechanisms that are used for development of new therapeutics. Application of Cryo-electron microscopy is not limited to protein complexes and is considered as non-specific. Intervention of Cryo-EM would allow to analyse the structures and also able to dissect the interaction with therapeutic molecules. The study determines the usage of cryo-EM for providing resolutions that are acceptable for lead discovery. It also provides support for lead optimization and also for discovery of vaccines and therapeutics.

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Isomalabaricane Triterpenes from the Marine Sponge Rhabdastrella sp.

Marine Drugs ◽

10.3390/md19040206 ◽

2021 ◽

Vol 19 (4) ◽

pp. 206

Author(s):

Kuei-Hung Lai ◽

Zheng-Hao Huang ◽

Mohamed El-Shazly ◽

Bo-Rong Peng ◽

Wen-Chi Wei ◽

...

Keyword(s):

Marine Sponge ◽

Structural Features ◽

Chemical Diversity ◽

Leukemic Cells ◽

Lead Discovery ◽

Proliferative Assay

The marine sponge of the genus Geodia, Jaspis, Rhabdastrella, and Stelletta are characterized chemically by a variety of isomalabaricane triterpenes. This class of compounds drew spotlights in marine lead discovery due to their profound anti-proliferative properties. Further research on exploring its chemical diversity led to the identifications of two new isomalabaricane-type triterpenes rhabdastin H (1) and rhabdastin I (2). Their structures were unraveled using a series of spectroscopic approaches. These isolates were found to exhibit unique structural features with the only reported tetrahydrofuran functionality among all marine-derived isomalabaricanes. Both compounds 1 and 2 showed activities against K562 (IC50 11.7 and 9.8 μM) and Molt4 (IC50 16.5 and 11.0 μM) leukemic cells in MTT cell proliferative assay.

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