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. 2016 Apr 12;21(4):420.
doi: 10.3390/molecules21040420.

Hybrid Compounds Strategy in the Synthesis of Oleanolic Acid Skeleton-NSAID Derivatives

Anna Pawełczyk  1 , Dorota Olender  2 , Katarzyna Sowa-Kasprzak  3 , Lucjusz Zaprutko  4
Affiliations

Hybrid Compounds Strategy in the Synthesis of Oleanolic Acid Skeleton-NSAID Derivatives

Anna Pawełczyk et al. Molecules. .

Abstract

The current study focuses on the synthesis of several hybrid individuals combining a natural oleanolic acid skeleton and synthetic nonsteroidal anti-inflammatory drug moieties (NSAIDs). It studied structural modifications of the oleanolic acid structure by use of the direct reactivity of hydroxyl or hydroxyimino groups at position C-3 of the triterpenoid skeleton with the carboxylic function of anti-inflammatory drugs leading to new perspective compounds with high potential pharmacological activities. Novel ester- and iminoester-type derivatives of oleanolic unit with the different NSAIDs, such as ibuprofen, aspirin, naproxen, and ketoprofen, were obtained and characterized. Moreover, preliminary research of compounds obtaining structure stability under acidic conditions was examined and the PASS method of prediction of activity spectra for substances was used to estimate the potential biological activity of these compounds.

Keywords: NSAIDs; aspirin; hybrid compounds; ibuprofen; ketoprofen; naproxen; oleanolic acid; oleanolic oxime.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
General integration modes of active dual structures. (A) Direct no-linker mode (fused hybrids); (B) Intermediate linker mode; (C) Overlap mode (merged hybrids).
Scheme 1
Scheme 1
Oleanolic acid transformations. Reagents and condition: (a) (CH3)2SO4, NaOH, EtOH, reflux; (b) Jones reagent, acetone, RT; and(c) NH2OH × HCl, CH3COONa, EtOH, reflux.
Figure 2
Figure 2
NSAID molecules selected.
Scheme 2
Scheme 2
The main chemical directions of oleanolic acid-NSAID compounds synthesis. Reagents and condition: (a) ester-type hybrids: DCC, DMAP, anhyd. CHCl3, RT; and (b) iminoester-type hybrid: DCC, anhyd. CHCl3, RT.
Figure 3
Figure 3
Formulas of the final hybrid derivatives obtained.
See this image and copyright information in PMC

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