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

Anna Pawełczyk,Dorota Olender,Katarzyna Sowa-Kasprzak,Lucjusz Zaprutko

doi:10.3390/molecules21040420

Anna Pawełczyk, Dorota Olender + Show 2 more

Open Access

https://doi.org/10.3390/molecules21040420

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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.

Highlights

Many scientific reports on the future prospects for the design of potentially useful drugs have been published
Chemical association of two structures into one new dual molecule depends on their functionality and cross-reactivity, and can be implemented by way of various methods [2,3]; Generally, the most popular molecules integration modes are: direct no-linker mode A; intermediate linker mode, B; and overlap mode, C (Figure 1)
The secondary hydroxyl group at theofC-3 of acid the oleanolic reacted in thereacted oxidation with chromic anhydride in sulfuricinacid (Jones to give skeleton was in theprocess oxidation process with chromic anhydride sulfuric acidreagent)

Summary

Introduction

Many scientific reports on the future prospects for the design of potentially useful drugs have been published. A hybrid compound is a synthetic product combining two or more separate active structures (or structure fragments) joined by at least one chemical bond. The unlimited possibilities of combining natural or unnatural active compounds can be exploited to generate individuals with unprecedented bioactivity and an additional potential synergic effect. The use of hybrids for disease treatment could offer several advantages, such as increased solubility, and several mechanisms of action in one molecule. This approach can be used to optimize certain biological properties, like affinity and selectivity, and to produce novel biological activities distinct from those of the components

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Conclusion