L-735,334, a Novel Sesquiterpenoid Potassium Channel-Agonist from Trichoderma virens

Lee, Seok H.; Hensens, Otto D.; Helms, Gregory L.; Liesch, Jerrold M.; Zink, Deborah L.; Giacobbe, Robert A.; Bills, Gerald F.; Stevens-Miles, Siobhan; García, María L.; Schmalhofer, William A.; McManus, Owen B.; Kaczorowski, Gregory J.

doi:10.1021/np50126a004

Cited by 27 publications

(20 citation statements)

References 2 publications

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“…Terpenoids such as dehydrosoyasaponin I (McManus et al, 1993), maxikdiol (Singh et al, 1994), and L-735,334 (Lee et al, 1995) have been identified as BK channel openers by use of 125 I-ChTX binding assay. Despite the structural dissimilarity, these three terpenoids share biological profiles; they can displace 125 I-ChTX, but not fully, and activate BK channel only when applied intracellularly in electrophysiological experiments.…”

Section: Discussionmentioning

confidence: 99%

Molecular Basis of Pimarane Compounds as Novel Activators of Large-Conductance Ca²⁺-Activated K⁺Channel α-Subunit

et al. 2002

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Effects of pimaric acid (PiMA) and eight closely related compounds on large-conductance K ϩ (BK) channels were examined using human embryonic kidney (HEK) 293 cells, in which either the ␣ subunit of BK channel (HEKBK␣) or both ␣ and ␤1 (HEKBK␣␤1) subunits were heterologously expressed. Effects of these compounds (10 M) on the membrane potential of HEKBK␣␤1 were monitored by use of DiBAC 4 (3), a voltagesensitive dye. PiMA, isopimaric acid, sandaracoisopimaric acid, dihydropimaric acid, dihydroisopimaric acid, and dihydroisopimarinol induced substantial membrane hyperpolarization. The direct measurement of BK␣␤1 opening under whole-cell voltage clamp showed that these six compounds activated BK␣␤1 in a very similar concentration range (1-10 M); in contrast, abietic acid, sclareol, and methyl pimarate had no effect. PiMA did not affect the charybdotoxin-induced block of macroscopic BK␣␤1 current. Single channel recordings of BK␣␤1 in insideout patches showed that 10 M PiMA did not change channel conductance but significantly increased its open probability as a result of increase in sensitivity to Ca 2ϩ and voltage. Because coexpression of the ␤1 subunit did not affect PiMA-induced potentiation, the site of action for PiMA is suggested to be BK␣ subunit. PiMA was selective to BK over cloned small and intermediate Ca 2ϩ activated K ϩ channels. In conclusion, PiMA (Ͼ1 M) increases Ca 2ϩ and voltage-sensitivity of BK␣ when applied from either side of the cell membrane. The marked difference in potency as BK channel openers between PiMA and abietic acid, despite only very small differences in their chemical structures, may provide insight into the fundamental structure-activity relationship governing BK␣ activation.

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Section: Discussionmentioning

confidence: 99%

Molecular Basis of Pimarane Compounds as Novel Activators of Large-Conductance Ca²⁺-Activated K⁺Channel α-Subunit

et al. 2002

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“…3) exhibiting antifungal activity against various yeast and dermatophytes and having a remarkable effect on Candida albicans (Watanabe et al 1990). Lee et al (1995a) isolated an oleic ester derivative of 8 named L-735,334 (9) (Fig. 3), from T. virens grown in several culture broths.…”

Section: Daucanesmentioning

confidence: 99%

“…3), from T. virens grown in several culture broths. Both metabolites, 8 and 9, are modulators of the high conductance calcium-activated potassium channel (Ondeyka et al 1995;Lee et al 1995a). Four new metabolites with carotane skeletons, trichocaranes A-D (10-13) (Fig.…”

Section: Daucanesmentioning

confidence: 99%

Secondary metabolites from species of the biocontrol agent Trichoderma

et al. 2007

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Trichoderma species are free-living fungi that are highly interactive in root, soil and foliar environments and have been used successfully in field trials to control many crop pathogens. Structural and biological studies of the metabolites isolated from Trichoderma species are reviewed. This review, encompassing all the literature in this field up to the present and in which 269 references are cited, also includes a detailed study of the biological activity of the metabolites, especially the role of these metabolites in biological control mechanisms. Some aspects of the biosynthesis of these metabolites and related compounds are likewise discussed.

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“…By using [McManus et al, 1993], maxikdiol [Singh et al, 1994], and L-735,334 [Lee et al, 1995b]. While DHS-1 was considerably more potent than maxikdiol and L-735,334 in binding and functional assays, they all opened the BK channels only when applied at the intracellular side of the membrane.…”

Section: Introductionmentioning

confidence: 99%

Novel and potent BK channel openers: CGS 7181 and its analogs

Fink

Kim

et al. 1997

Drug Dev. Res.

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L-735,334, a Novel Sesquiterpenoid Potassium Channel-Agonist from Trichoderma virens

Cited by 27 publications

References 2 publications

Molecular Basis of Pimarane Compounds as Novel Activators of Large-Conductance Ca²⁺-Activated K⁺Channel α-Subunit

Molecular Basis of Pimarane Compounds as Novel Activators of Large-Conductance Ca²⁺-Activated K⁺Channel α-Subunit

Secondary metabolites from species of the biocontrol agent Trichoderma

Novel and potent BK channel openers: CGS 7181 and its analogs

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L-735,334, a Novel Sesquiterpenoid Potassium Channel-Agonist from Trichoderma virens

Cited by 27 publications

References 2 publications

Molecular Basis of Pimarane Compounds as Novel Activators of Large-Conductance Ca2+-Activated K+Channel α-Subunit

Molecular Basis of Pimarane Compounds as Novel Activators of Large-Conductance Ca2+-Activated K+Channel α-Subunit

Secondary metabolites from species of the biocontrol agent Trichoderma

Novel and potent BK channel openers: CGS 7181 and its analogs

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Product

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Molecular Basis of Pimarane Compounds as Novel Activators of Large-Conductance Ca²⁺-Activated K⁺Channel α-Subunit

Molecular Basis of Pimarane Compounds as Novel Activators of Large-Conductance Ca²⁺-Activated K⁺Channel α-Subunit