1. OF PLANT N-ALKYLAMIDES
1.1. Structure
1.2. Occurrence
1.3. Objective
2. Database
3. Clustering
4. Conclusions
CHEMICAL-FUNCTIONAL SPACE EXPLORATION
OF PLANT N-ALKYLAMIDES
Jente Boonen1, Vikas Sharma2, Vinot Dixit2 and Bart De Spiegeleer1*
1 Drug Quality and Registration (DruQuaR) group, Faculty of Pharmaceutical Sciences,
Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium
2 Department of Pharmaceutical Sciences, Dr. H.S. Gour University, Sagar M.P. India.
*Corresponding author: Tel.: ; Fax: , b

2. N-Alkylamides
1.1. Structure
1.2. Occurrence
1.3. Objective
2. Database
3. Clustering
4. Conclusions
R1=
Aliphatic, often unsaturated units, w/wo substutients (N, O, S, cyclic,…) or in cyclic system with R2.
R2=
Aliphatic, often isobutylamide, methylbutylamide, phenylethylamide, tyramide, piperidide or pyrrolidide derivative, w/wo substituents (N, O, S, cyclic,…) or in cyclic system with R1.
R3=
Mostly H, Me, MeO, OH function.
New group of potential drugs related to lipoid peptides (anti-inflammatory, immunostimulant, anti-hepatotoxic, anti-oxidant, tingling, CB2 endocannabinomimetic, anti-microbial,…)
May 2011

3. Now: 9 different plant families
N-Alkylamides
1.1. Structure
1.2. Occurrence
1.3. Objective
2. Database
3. Clustering
4. Conclusions
Ceramides Ergopeptides
R= aliphatic chain
May 2011

4. No structured overview of plant N-alkylamides?
N-Alkylamides
1.1. Structure
1.2. Occurrence
1.3. Objective
2. Database
3. Clustering
4. Conclusions
Plant species N-alkylamide
Functionality ? ?
Interdisciplinary
No structured overview of plant N-alkylamides
DATABASE
CHEMICAL CLUSTERING
May 2011

5. Relational database, now containing ± 300 plant N-alkylamides
CC(C)CNC(=O)\C=C\CC/C=C\C=C\C
C14H23NO
deca-2E,6Z,8E-trienoic acid isobutylamide
(2E,4E,8E)-N-butan-2-yldeca-2,4,8-trienamide
spilanthol or affinin
Asteraceae
Helianthea
Spilanthes
acmella
Anti-oxidant
EC50=1.38 µmol
N-Alkylamides
2. Database
3. Clustering
4. Conclusions
May 2011

6. 3D structure optimization Calculation and selection of 141 descriptors
Constitutional descriptors
WHIM descriptors
Molecular properties
- Data-scaling transformation: zi = (хi – x)/SD
Multivariate analysis:
Hierarchical cluster analysis (HCA)
Principal compontent analysis (PCA)
N-Alkylamides
2. Database
3. Clustering
4. Conclusions
May 2011

7. HCA => Dendrogram PCA => PC1_PC2 (4 PCs for >70% Q²)
1. N-Alkylamides
2. Database
3. Clustering
4. Conclusions
HCA => Dendrogram
PCA => PC1_PC2
(4 PCs for >70% Q²)
May 2011

8. Scoring plot Loading plot N-Alkylamides 2. Database 3. Clustering
4. Conclusions
Loading plot

9. QUALITY ATTRIBUTES FOR CLUSTER: (1) Constitutional
N-Alkylamides
2. Database
3. Clustering
4. Conclusions
QUALITY ATTRIBUTES FOR CLUSTER:
(1) Constitutional
AMW => molecular weight
nAB, nBnZ, nCIC, nRO6 => aromatic ring structures
(2) WHIM
P2: shape
L2: size
E2: accessibility
(3) Molecular properties
Ui => unsaturation index
«228»
«220»
«193»
May 2011

10. DATABASE => EXPLORATORY MINING
Chemical/functional overview of plant N-alkylamides
CLUSTERING
Chemical similarities =>
Functionality
Toxicity
PK e.g. transdermal/transmucosal
Justified choice of model compounds
N-Alkylamides
2. Database
3. Clustering
4. Conclusions
May 2011

11. Thank you for your attention
May 2011