Isolation of myosin light chain kinase inhibitors from microorganisms: dehydroaltenusin, altenusin, atrovenetinone, and cyclooctasulfur.
Dehydroaltenusin, cyclooctasulfur, atrovenetinone, and altenusin were isolated from the culture broths of Penicillium verruculosum IAM-13756, Streptomyces verticillus subsp. tskushiensis ATCC-21633, Penicillium sp. SPC-16375, and Penicillium sp. SPC-16524, respectively, as new myosin light chain kinase (MLCK) inhibitors. These compounds inhibited the calmodulin-dependent activity of MLCK with IC50 values of 0.69, 0.86, 3.7, and 350 microM, respectively. Among them, dehydroaltenusin was the best MLCK inhibitor in terms of potency and selectivity examined in the purified enzyme systems.
Nakanishi
S
S
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Japan.
Toki
S
S
Saitoh
Y
Y
Tsukuda
E
E
Kawahara
K
K
Ando
K
K
Matsuda
Y
Y
D001578:Benzopyrans / Q000302:isolation & purification* / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000302:isolation & purification* / Q000494:pharmacology; D002147:Calmodulin / Q000737:chemistry; D006633:Histamine Antagonists / Q000494:pharmacology*; D006868:Hydrolysis; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors*; D009281:Naphthalenes / Q000302:isolation & purification* / Q000494:pharmacology; D010407:Penicillium / Q000378:metabolism*; D013302:Streptomyces / Q000378:metabolism*; D013455:Sulfur / Q000302:isolation & purification* / Q000494:pharmacology; D014357:Trypsin / Q000737:chemistry
D001578:Benzopyrans; D001713:Biphenyl Compounds; D002147:Calmodulin; D006633:Histamine Antagonists; D009281:Naphthalenes; C095644:atrovenetinone; C056471:cyclooctasulfur; C095643:altenusin; D013455:Sulfur; D009219:Myosin-Light-Chain Kinase; D014357:Trypsin; C095645:dehydroaltenusin