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 [125I]omega-conotoxin MVIIA binding to N-type Ca2+ channels (IC50= 0.17, 0.091 and 0.071 microM), but did not inhibit [3H]PN200-110 binding to L-type Ca2+ channels (IC50 > 50 microM). These compounds also inhibited [3H]norepinephrine release from chick cerebral cortex synaptosomes (IC50=91.0, 20.6 and 39.5 microM), 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.
Hisamoto
M
M
Neuroscience Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Inaoka
Y
Y
Sakaida
Y
Y
Kagazaki
T
T
Enokida
R
R
Okazaki
T
T
Haruyama
H
H
Kinoshita
T
T
Matsuda
K
K
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D002645:Chickens; D005658:Fungi / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D013302:Streptomyces / Q000737:chemistry* / Q000145:classification; D013309:Streptothricins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D020960:omega-Conotoxins
C114129:A 53930B; D002121:Calcium Channel Blockers; D010455:Peptides; D020960:omega-Conotoxins; C019594:racemomycin; D013309:Streptothricins; C078452:ziconotide; D009638:Norepinephrine