A-53930A and B, Novel N-Type Ca²⁺ Channel Blockers

Abstract

A-53930A, B and C, which inhibit N-type Ca²⁺ channels, were isolated from the culture broth of Streptomyces vinaceusdrappus SANK 62394. A-53930A and B were new compounds which contained a carbamoyl group on the 6-hydroxyl group of the D-gulosamine part of streptothricin. A-53930C was identical to streptothricin B. A-53930A, B and C inhibited [¹²⁵I]ω-conotoxin MVIIA binding to N-type Ca²⁺ channels (IC₅₀=0.17, 0.091 and 0.071 μM), but did not inhibit [³H]PN200-110 binding to L-type Ca²⁺ channels (IC₅₀>50 μM). These compounds also inhibited [³H]norepinephrine release from chick cerebral cortex synaptosomes (IC₅₀=91.0, 20.6 and 39.5 μM), indicating these compounds selectively block N-type Ca²⁺ channels which are important for neurotransmitter release. It was also revealed that although A-53930C had antimicrobial activity against Gram-negative and -positive bacteria and fungi, A-53930A and B showed weak activity only against Gram-negative bacteria.