Isolation of a library of aromadendranes from Landolphia dulcis and its characterization using the VolSurf approach
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Isolation of a library of aromadendranes from Landolphia dulcis and its characterization using the VolSurf approach. / Staerk, Dan; Skole, Brian; Jørgensen, Flemming Steen; Budnik, Bogdan A; Ekpe, Patrick; Jaroszewski, Jerzy W.
I: Journal of Natural Products, Bind 67, Nr. 5, 2004, s. 799-805.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Isolation of a library of aromadendranes from Landolphia dulcis and its characterization using the VolSurf approach
AU - Staerk, Dan
AU - Skole, Brian
AU - Jørgensen, Flemming Steen
AU - Budnik, Bogdan A
AU - Ekpe, Patrick
AU - Jaroszewski, Jerzy W
PY - 2004
Y1 - 2004
N2 - A library of nine aromadendrane-type sesquiterpenes (1-9), including eight new natural products (1-5 and 7-9), was isolated from Landolphia dulcis var. barteri along with a previously described cadinane derivative (10) and a new muurolane derivative (11). The structures of all compounds were established by means of NMR methods including COSY, NOESY, HSQC, and HMBC experiments, supported by HRMS and optical rotation data. Virtual characterization of the aromadendrane library (1-9) was performed using chemoinformatics tools. 3D molecular fields were calculated with the GRID program using low-energy structures obtained with the MMFF force field. VolSurf descriptors were calculated from the GRID maps and subsequently analyzed by multivariate statistics. The analysis disclosed the presence of a common motif for possible interactions of the aromadendranes with a putative target receptor. At the same time, a considerable chemical diversity within the library was disclosed, despite a close biosynthetic relationship of its members. The results can be interpreted in terms of evolutionary optimization of structures of secondary metabolites for interaction with macromolecular targets and are of interest in terms of assessment of potential "drug-likeness" of natural products.
AB - A library of nine aromadendrane-type sesquiterpenes (1-9), including eight new natural products (1-5 and 7-9), was isolated from Landolphia dulcis var. barteri along with a previously described cadinane derivative (10) and a new muurolane derivative (11). The structures of all compounds were established by means of NMR methods including COSY, NOESY, HSQC, and HMBC experiments, supported by HRMS and optical rotation data. Virtual characterization of the aromadendrane library (1-9) was performed using chemoinformatics tools. 3D molecular fields were calculated with the GRID program using low-energy structures obtained with the MMFF force field. VolSurf descriptors were calculated from the GRID maps and subsequently analyzed by multivariate statistics. The analysis disclosed the presence of a common motif for possible interactions of the aromadendranes with a putative target receptor. At the same time, a considerable chemical diversity within the library was disclosed, despite a close biosynthetic relationship of its members. The results can be interpreted in terms of evolutionary optimization of structures of secondary metabolites for interaction with macromolecular targets and are of interest in terms of assessment of potential "drug-likeness" of natural products.
KW - Apocynaceae
KW - Combinatorial Chemistry Techniques
KW - Ghana
KW - Molecular Conformation
KW - Molecular Structure
KW - Nuclear Magnetic Resonance, Biomolecular
KW - Plant Roots
KW - Sesquiterpenes
KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
U2 - 10.1021/np0340450
DO - 10.1021/np0340450
M3 - Journal article
C2 - 15165140
VL - 67
SP - 799
EP - 805
JO - Journal of Natural Products
JF - Journal of Natural Products
SN - 0163-3864
IS - 5
ER -
ID: 38393998