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

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 [I-125]omega-conotoxin MVIIA binding to N-type Ca2+ channels (IC50 = 0.17, 0.091 and 0.071 mu M), but did not inhibit [H-3]PN200-110 binding to L-type Ca2+ channels (IC50> 50 mu M). These compounds also inhibited [H-3]norepinephrine release from chick cerebral cortex synaptosomes (IC50 = 91.0, 20.6 and 39.5 mu M), 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.