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A-53930A and B, novel N-type Ca2+ channel blockers

M Hisamoto1, Y Inaoka, Y Sakaida

  • 1Neuroscience Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.

The Journal of Antibiotics
|September 4, 1998
PubMed
Summary

New compounds A-53930A and B, isolated from Streptomyces, selectively inhibit N-type calcium channels, crucial for neurotransmitter release. Compound A-53930C also showed this activity and possessed antimicrobial properties.

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Area of Science:

  • Pharmacology
  • Microbiology
  • Neuroscience

Background:

  • Streptomyces vinaceusdrappus SANK 62394 produces novel compounds.
  • N-type calcium channels are vital for neurotransmission.

Purpose of the Study:

  • To isolate and characterize compounds from Streptomyces vinaceusdrappus.
  • To investigate the inhibitory effects of these compounds on calcium channels and neurotransmitter release.

Main Methods:

  • Isolation of compounds A-53930A, B, and C from culture broth.
  • Assay of [125I]omega-conotoxin MVIIA binding to N-type Ca2+ channels.
  • Assay of [3H]PN200-110 binding to L-type Ca2+ channels.
  • Measurement of [3H]norepinephrine release from synaptosomes.

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Main Results:

  • A-53930A and B are new streptothricin derivatives; A-53930C is identical to streptothricin B.
  • Compounds A-53930A, B, and C selectively inhibited N-type Ca2+ channels (IC50s 0.17, 0.091, 0.071 μM) but not L-type channels.
  • These compounds inhibited norepinephrine release from synaptosomes (IC50s 91.0, 20.6, 39.5 μM).
  • A-53930C exhibited broad antimicrobial activity, while A-53930A and B showed weak activity against Gram-negative bacteria.

Conclusions:

  • Compounds A-53930A, B, and C are potent and selective N-type calcium channel blockers.
  • These compounds have potential applications in modulating neurotransmitter release.
  • A-53930C possesses both channel blocking and antimicrobial activities.