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United States Department of Agriculture

Agricultural Research Service

Research Project: CONTROL OF TOXIC ENDOPHYTIC FUNGI WITH BACTERIAL ENDOPHYTES AND REGULATION OF BACTERIAL METABOLITES FOR NOVEL USES IN FOOD SAFETY

Location: Toxicology and Mycotoxin Research

Title: Hintoniamine, a new calmodulin inhibitor from the endophytic fungal species 39140-2

Authors
item Leyte-Lugo, Martha -
item Gonzalez-Andrade, Martin -
item Gonzalez Maria, Del Carmen -
item Glenn, Anthony
item Mata, Rachel -

Submitted to: American Society of Pharmacognosy
Publication Type: Abstract Only
Publication Acceptance Date: March 15, 2011
Publication Date: N/A

Interpretive Summary: Abstract - no summary required.

Technical Abstract: A new fungal endophytic species (39140-2) was isolated from the medicinal plant Hintonia latiflora (Sessé et Mociño ex DC.) Bullock, a Rubiaceae widely used in Mexico as antidiabetic agent. Sequencing of the 28S fraction of the rDNA of this fungal strain and comparing with similar sequences for all fungi in the NCBI GenBank database revealed no matches. Therefore endophyte 39140-2 is a new fungus. Endophyte 39140-2 was grown in liquid-substrate on PDA medium, at room temperature and static conditions. After the fermentation, CH2Cl2 extracts were prepared from the mycelium and fermentation medium. Chromatographic separation of the combined extracts allowed the isolation of compound 1, which was given the trivial name of hintoniamine (1), after the genus of the plant. The 1H-NMR spectra of 1 in CDCl3 showed resonances for a disubstituted pyridine ring and a methylene group attached to oxygen. Also apparent in the 1H-NMR spectrum were resonances for a conjugated four carbons side chain possessing a methyl group attached to a trans double bond. Furthermore, it revealed the existence of an enol-enol equilibrium between the short-lived tautomers 1a and 1b (Figure 1). Hintoniamide was tested as potential calmodulin (CaM) inhibitor; the affinity of 1 by CaM was determined with the hCaM M124C-mBBr fluorescent biosensor. Compound 1 quenched significantly the extrinsic fluorescence of the biosensor, with a dissociation constant (Kd) value of 0.212 µM, better than that of chlorpromazine (CPZ; Kd= 1.2 µM), a classical CaM inhibitor.

Last Modified: 9/1/2014
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