A novel 24-membered polyene lactam macrolide, micromonosporin A (=(3E,5E,7Z,15E,17E,19E,21E)-9,11,13-trihydroxy-14,19,24-trimethyl-1-azacyclotetracosa-3,5,7,15,17,19,21-heptaen-2-one; 1) was isolated from the actinomycete, Micromonospora sp. strain TT1-11, which was isolated from a very acidic peat swamp forest.
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http://dx.doi.org/10.1002/cbdv.200490055 | DOI Listing |
Mar Drugs
October 2024
CAS Key Laboratory of Tropical Marine Bio-Resources, Ecology/Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
Three new 24-membered macrolactines, amylomacrolactines A-C (-), along with two known compounds and , were isolated from the Arctic bacteria SCSIO 41392. The configurations of - were assigned by a combination of coupling constants, NOESY, and analysis of MM2-optimized conformation, as well as by comparison with reports in the literature. Compounds and showed quorum sensing (QS) inhibitory activities against the PQS system and suppressed PQS-regulated virulence factor pyocyanin synthesis.
View Article and Find Full Text PDFMol Pharmacol
February 2024
Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee (A.G., T.Q.D. K.K., D.J.B., P.A.R., B.C.K.); Vanderbilt Department of Chemistry and Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee (M.P.T., A.N.S., J.N.J.); Pharmaceutical Sciences Research Center, Lipscomb University College of Pharmacy, Nashville, Tennessee (W.S.A.); Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota (J.A.S., R.L.C., R.T.R.); and School of Biomedical Sciences and Pharmacy, University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW 2308, Australia (D.R.L.)
Intracellular Ca leak from cardiac ryanodine receptor (RyR2) is an established mechanism of sudden cardiac death (SCD), whereby dysregulated Ca handling causes ventricular arrhythmias. We previously discovered the RyR2-selective inhibitor (+)-verticilide (-1), a 24-membered cyclooligomeric depsipeptide that is the enantiomeric form of a natural product (-(-)-verticilide). Here, we examined its 18-membered ring-size oligomer (-verticilide B1; "-B1") in RyR2 single channel and [H]ryanodine binding assays, and in cardiomyocytes and mice, a gene-targeted model of SCD.
View Article and Find Full Text PDFUnlabelled: Ca leak from cardiac ryanodine receptor (RyR2) is an established mechanism of sudden cardiac death (SCD), whereby dysregulated Ca handling causes ventricular arrhythmias. We previously discovered the RyR2-selective inhibitor (+)-verticilide ( -1), a 24-membered cyclooligomeric depsipeptide that is the enantiomeric form of a natural product ( -(-)-verticilide). Here, we examined its 18-membered ring-size oligomer ( -verticilide B1; " -B1") in single RyR2 channel assays, [ H]ryanodine binding assays, and in cardiomyocytes and mice, a gene-targeted model of SCD.
View Article and Find Full Text PDFBioorg Med Chem
November 2022
School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, China; Collaborative Innovation Center of Chinese Medicines from Zhejiang Province, China. Electronic address:
β-Elemene is the major constituent of the antitumor drugs elemene extract approved in China. By incorporating macrocyclization strategy into the β-elemene skeleton, we designed a series of novel macrocycles retaining three key carbon-carbon double bonds. Four different methods have been successfully developed for these challenging ring systems.
View Article and Find Full Text PDFMar Life Sci Technol
February 2021
Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003 China.
Marine microorganisms have proven to be a rich source of natural products with unique structures and novel activities, due to their special living conditions. Macrolactins (MLNs), mostly produced by marine-derived microorganisms, are a group of 24-membered lactone natural products, which exhibit potent antibacterial, antifungal, antiviral, anticancer, anti-inflammatory, anti-angiogenic and other activities. Their extensive biological activities make them potential compounds for drug development.
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