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 -