PMID- 30005573
OWN - NLM
STAT- MEDLINE
DCOM- 20190618
LR  - 20190618
IS  - 1520-4804 (Electronic)
IS  - 0022-2623 (Linking)
VI  - 61
IP  - 15
DP  - 2018 Aug 9
TI  - Design and Synthesis of Natural Product Inspired Libraries Based on the 
      Three-Dimensional (3D) Cedrane Scaffold: Toward the Exploration of 3D Biological 
      Space.
PG  - 6609-6628
LID - 10.1021/acs.jmedchem.8b00194 [doi]
AB  - A chemoinformatic method was developed to extract nonflat scaffolds embedded in 
      natural products within the Dictionary of Natural Products (DNP). The cedrane 
      scaffold was then chosen as an example of a nonflat scaffold that directs 
      substituents in three-dimensional (3D) space. A cedrane scaffold that has three 
      orthogonal handles to allow generation of 1D, 2D, and 3D libraries was 
      synthesized on a large scale. These libraries would cover more than 50% of the 
      natural diversity of natural products with an embedded cedrane scaffold. 
      Synthesis of three focused natural product-like libraries based on the 3D cedrane 
      scaffold was achieved. A phenotypic assay was used to test the biological profile 
      of synthesized compounds against normal and Parkinson's patient-derived cells. 
      The cytological profiles of the synthesized analogues based on the cedrane 
      scaffold revealed that this 3D scaffold, prevalidated by nature, can interact 
      with biological systems as it displayed various effects against normal and 
      Parkinson's patient-derived cell lines.
FAU - Mazraati Tajabadi, Fatemeh
AU  - Mazraati Tajabadi F
AD  - Griffith Institute for Drug Discovery , Griffith University , Brisbane , QLD 4111 
      , Australia.
FAU - Pouwer, Rebecca H
AU  - Pouwer RH
AD  - Griffith Institute for Drug Discovery , Griffith University , Brisbane , QLD 4111 
      , Australia.
FAU - Liu, Miaomiao
AU  - Liu M
AD  - Griffith Institute for Drug Discovery , Griffith University , Brisbane , QLD 4111 
      , Australia.
FAU - Dashti, Yousef
AU  - Dashti Y
AD  - Griffith Institute for Drug Discovery , Griffith University , Brisbane , QLD 4111 
      , Australia.
FAU - Campitelli, Marc R
AU  - Campitelli MR
AD  - Griffith Institute for Drug Discovery , Griffith University , Brisbane , QLD 4111 
      , Australia.
FAU - Murtaza, Mariyam
AU  - Murtaza M
AD  - Griffith Institute for Drug Discovery , Griffith University , Brisbane , QLD 4111 
      , Australia.
FAU - Mellick, George D
AU  - Mellick GD
AD  - Griffith Institute for Drug Discovery , Griffith University , Brisbane , QLD 4111 
      , Australia.
FAU - Wood, Stephen A
AU  - Wood SA
AD  - Griffith Institute for Drug Discovery , Griffith University , Brisbane , QLD 4111 
      , Australia.
FAU - Jenkins, Ian D
AU  - Jenkins ID
AD  - Griffith Institute for Drug Discovery , Griffith University , Brisbane , QLD 4111 
      , Australia.
FAU - Quinn, Ronald J
AU  - Quinn RJ
AUID- ORCID: 0000-0002-4022-2623
AD  - Griffith Institute for Drug Discovery , Griffith University , Brisbane , QLD 4111 
      , Australia.
LA  - eng
PT  - Journal Article
DEP - 20180727
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Biological Products)
SB  - IM
MH  - Biological Products/*chemistry
MH  - Biomimetic Materials/*chemical synthesis/*chemistry/pharmacology
MH  - Cell Line
MH  - Chemistry Techniques, Synthetic
MH  - *Drug Design
MH  - Humans
MH  - *Informatics
MH  - Models, Molecular
MH  - Molecular Conformation
MH  - Phenotype
EDAT- 2018/07/15 06:00
MHDA- 2019/06/19 06:00
CRDT- 2018/07/15 06:00
PHST- 2018/07/15 06:00 [pubmed]
PHST- 2019/06/19 06:00 [medline]
PHST- 2018/07/15 06:00 [entrez]
AID - 10.1021/acs.jmedchem.8b00194 [doi]
PST - ppublish
SO  - J Med Chem. 2018 Aug 9;61(15):6609-6628. doi: 10.1021/acs.jmedchem.8b00194. Epub 
      2018 Jul 27.