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Review
. 2022 Oct 3;27(19):6552.
doi: 10.3390/molecules27196552.

Semisynthetic Derivatives of Pentacyclic Triterpenes Bearing Heterocyclic Moieties with Therapeutic Potential

Gabriela Nistor  1   2 , Cristina Trandafirescu  1   2 , Alexandra Prodea  1   2 , Andreea Milan  1   2 , Andreea Cristea  1   2 , Roxana Ghiulai  1   2 , Roxana Racoviceanu  1   2 , Alexandra Mioc  2   3 , Marius Mioc  1   2 , Viviana Ivan  4 , Codruța Șoica  1   2
Affiliations
Review

Semisynthetic Derivatives of Pentacyclic Triterpenes Bearing Heterocyclic Moieties with Therapeutic Potential

Gabriela Nistor et al. Molecules. .

Abstract

Medicinal plants have been used by humans since ancient times for the treatment of various diseases and currently represent the main source of a variety of phytocompounds, such as triterpenes. Pentacyclic triterpenes have been subjected to numerous studies that have revealed various biological activities, such as anticancer, antidiabetic, anti-inflammatory, antimicrobial, and hepatoprotective effects, which can be employed in therapy. However, due to their high lipophilicity, which is considered to exert a significant influence on their bioavailability, their current use is limited. A frequent approach employed to overcome this obstacle is the chemical derivatization of the core structure with different types of moieties including heterocycles, which are considered key elements in medicinal chemistry. The present review aims to summarize the literature published in the last 10 years regarding the derivatives of pentacyclic triterpenes bearing heterocyclic moieties and focuses on the biologically active derivatives as well as their structure-activity relationships. Predominantly, the targeted positions for the derivatization of the triterpene skeleton are C-3 (hydroxyl/oxo group), C-28 (hydroxyl/carboxyl group), and C-30 (allylic group) or the extension of the main scaffold by fusing various heterocycles with the A-ring of the phytocompound. In addition, numerous derivatives also contain linker moieties that connect the triterpenic scaffold with heterocycles; one such linker, the triazole moiety, stands out as a key pharmacophore for its biological effect. All these studies support the hypothesis that triterpenoid conjugates with heterocyclic moieties may represent promising candidates for future clinical trials.

Keywords: betulin; betulinic acid; betulonic acid; bioconjugates; corosolic acid; heterocycles; lupeol; maslinic acid; oleanolic acid; pentacyclic triterpenes; structure–activity relationship; ursolic acid.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Frequent targets for the derivatization of lupeol.
Figure 2
Figure 2
Frequent targets for the derivatization of betulin.
Figure 3
Figure 3
Frequent targets for the derivatization of betulinic acid.
Figure 4
Figure 4
The chemical structure of P-BA and P-SS-BA (the red circle highlights the unbreakable bonds and the green circle highlights the breakable disulfide bonds in the given conditions).
Figure 5
Figure 5
Derivatives of BA and OA with alpha-CD.
Figure 6
Figure 6
Frequent targets for the derivatization of betulonic acid.
Figure 7
Figure 7
Frequent targets for the derivatization of ursolic acid.
Figure 8
Figure 8
Frequent targets for the derivatization of maslinic acid.
Figure 9
Figure 9
Frequent targets for the derivatization of corosolic acid.
Figure 10
Figure 10
The chemical structure of MA 1.
Figure 11
Figure 11
Frequent targets for the derivatization of oleanolic acid.
See this image and copyright information in PMC

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