ABSTRACT
In the course of our screening efforts to discover small molecules as selective inhibitors of vacuolar-type H+-ATPase of Saccharomyces cerevisiae, we have identified eight active destruxins, 1-8, from the fungus Metarhizium anisopliae. The structures were elucidated by extensive 1D- and 2D-NMR spectroscopy, and MS spectrometry. One of these compounds, 8, a regioisomer of chlorohydrin destruxin E (7), is a new destruxin.
Subject(s)
Depsipeptides/metabolism , Depsipeptides/pharmacology , Saccharomyces cerevisiae/enzymology , Vacuolar Proton-Translocating ATPases/antagonists & inhibitors , Animals , Chickens , Dose-Response Relationship, Drug , Fermentation , Inhibitory Concentration 50 , Metarhizium/metabolism , Molecular Structure , Osteoclasts , Time Factors , Vacuolar Proton-Translocating ATPases/metabolismABSTRACT
In the course of a search for small-molecule inhibitors of 5-hydroxytryptamine receptors we have identified a novel ergoline derivative (1) from the fungal culture of Dicyma sp. This compound has a pK(i) of 10.2 versus the 5-hydroxytryptamine(1A) receptor subtype. The structure was elucidated by extensive NMR spectroscopy and mass spectrometry.
Subject(s)
Ascomycota/chemistry , Ergolines/isolation & purification , Ergot Alkaloids/isolation & purification , Receptor, Serotonin, 5-HT1A/drug effects , Serotonin Antagonists/isolation & purification , Animals , Brain/drug effects , Brain/metabolism , Brain/ultrastructure , Cell Membrane/drug effects , Cell Membrane/metabolism , Ergolines/chemistry , Ergolines/pharmacology , Ergot Alkaloids/chemistry , Ergot Alkaloids/pharmacology , Guanosine 5'-O-(3-Thiotriphosphate)/metabolism , In Vitro Techniques , Magnetic Resonance Spectroscopy , Radioligand Assay , Receptor, Serotonin, 5-HT1A/metabolism , Serotonin Antagonists/chemistry , Serotonin Antagonists/pharmacologyABSTRACT
The increasing size of the collections used for drug-discovery purposes has demanded both hardware and software automation of compound management in order to cope with the increasing demands of HTS. Splitting the collection into a number of copies in different formats is a desirable approach to keep a balance between rapid response to the demands and best storage conditions. Flexibility to different assay configurations can be provided with the appropriate selection of liquid handlers, and the informatic management systems should be accessible to keep track of the samples and link them to a variety of information that can help interpret HTS data. In this respect, QC data on the compounds and quality checks of the equipment used are highly desirable. It is also prudent for a large organization with different research sites to have a unified database and compatible plate format and concentration in order to be able to exchange samples and share screening results. The accomplishment of all the previous requirements is the only way to ensure an efficient and effective compound library management.