PMID- 29168322
OWN - NLM
STAT- MEDLINE
DCOM- 20171218
LR  - 20180423
IS  - 1860-7187 (Electronic)
IS  - 1860-7179 (Linking)
VI  - 12
IP  - 23
DP  - 2017 Dec 7
TI  - Biosynthetically Guided Structure-Activity Relationship Studies of Merochlorin A, 
      an Antibiotic Marine Natural Product.
PG  - 1969-1976
LID - 10.1002/cmdc.201700451 [doi]
AB  - The onset of new multidrug-resistant strains of bacteria demands continuous 
      development of antibacterial agents with new chemical scaffolds and mechanisms of 
      action. We present the first structure-activity relationship (SAR) study of 16 
      derivatives of a structurally novel antibiotic merochlorin A that were designed 
      using a biosynthetic blueprint. Our lead compounds are active against several 
      Gram-positive bacteria such as Staphylococcus aureus (SA), methicillin-resistant 
      Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE) and 
      Bacillus subtilis, inhibit intracellular growth of Mycobacterium bovis, and are 
      relatively nontoxic to human cell lines. Furthermore, derivative 12 c 
      (+/-)-(3aR,4S,5R,10bS)-5-bromo-7,9-dimethoxy-4-methyl-4-(4-methylpent-3-en-1-yl)-2-(propan-2-ylidene)-1,2,3,3a,4,5-hexahydro-6H-5,10b-methanobenzo[e]azulene-6,11-dione 
      was found to inhibit the growth of Bacillus Calmette-Guerin (BCG)-infected cells 
      at concentrations similar to rifampicin. These results outperform the natural 
      product, underscoring the potential of merochlorin analogues as a new class of 
      antibiotics.
CI  - (c) 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Lopez-Perez, Borja
AU  - Lopez-Perez B
AD  - Department of Chemistry, University of Adelaide, Adelaide, South Australia, 5005, 
      Australia.
FAU - Pepper, Henry P
AU  - Pepper HP
AD  - Department of Chemistry, University of Adelaide, Adelaide, South Australia, 5005, 
      Australia.
FAU - Ma, Rong
AU  - Ma R
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, Shanghai, 200237, China.
FAU - Fawcett, Benjamin J
AU  - Fawcett BJ
AD  - Department of Chemistry, University of Adelaide, Adelaide, South Australia, 5005, 
      Australia.
FAU - Pehere, Ashok D
AU  - Pehere AD
AD  - Department of Chemistry, University of Adelaide, Adelaide, South Australia, 5005, 
      Australia.
FAU - Wei, Qi
AU  - Wei Q
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, Shanghai, 200237, China.
AD  - College of Life Science, Hebei University, Baoding, 071002, P.R. China.
FAU - Ji, Zengchun
AU  - Ji Z
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, Shanghai, 200237, China.
AD  - School of Biological Engineering, Tianjin University of Science and Technology, 
      Tianjin, 300457, P.R. China.
FAU - Polyak, Steven W
AU  - Polyak SW
AD  - Department of Molecular and Cellular Biology, University of Adelaide, Adelaide, 
      South Australia, 5005, Australia.
FAU - Dai, Huanqin
AU  - Dai H
AD  - Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and 
      Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 
      100101, China.
FAU - Song, Fuhang
AU  - Song F
AD  - Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and 
      Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 
      100101, China.
FAU - Abell, Andrew D
AU  - Abell AD
AD  - Department of Chemistry, University of Adelaide, Adelaide, South Australia, 5005, 
      Australia.
AD  - Centre for Nanoscale Biophotonics, CNBP, University of Adelaide, Adelaide, South 
      Australia, 5005, Australia.
FAU - Zhang, Lixin
AU  - Zhang L
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, Shanghai, 200237, China.
AD  - Key Biosensor Laboratory of Shandong Province, Biology Institute, Shandong 
      Academy of Sciences, Jinan, 250014, China.
AD  - Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for 
      Marine Science and Technology, Qingdao, 266061, China.
FAU - George, Jonathan H
AU  - George JH
AUID- ORCID: 0000-0002-7330-2160
AD  - Department of Chemistry, University of Adelaide, Adelaide, South Australia, 5005, 
      Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171123
PL  - Germany
TA  - ChemMedChem
JT  - ChemMedChem
JID - 101259013
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Biological Products)
RN  - 0 (Sesterterpenes)
RN  - 0 (merochlorin A)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/biosynthesis/chemistry/*pharmacology
MH  - Biological Products/chemistry/metabolism/*pharmacology
MH  - Cell Line
MH  - Dose-Response Relationship, Drug
MH  - Erythrocytes/*drug effects/microbiology
MH  - Gram-Positive Bacteria/*drug effects
MH  - Horses
MH  - Microbial Sensitivity Tests
MH  - Molecular Conformation
MH  - Sesterterpenes/biosynthesis/chemistry/*pharmacology
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - BCG
OT  - MRSA
OT  - antibiotics
OT  - natural products
OT  - structure-activity relationships
EDAT- 2017/11/24 06:00
MHDA- 2017/12/19 06:00
CRDT- 2017/11/24 06:00
PHST- 2017/08/01 00:00 [received]
PHST- 2017/11/24 06:00 [pubmed]
PHST- 2017/12/19 06:00 [medline]
PHST- 2017/11/24 06:00 [entrez]
AID - 10.1002/cmdc.201700451 [doi]
PST - ppublish
SO  - ChemMedChem. 2017 Dec 7;12(23):1969-1976. doi: 10.1002/cmdc.201700451. Epub 2017 
      Nov 23.