Chemical Strategies towards the Synthesis of Betulinic Acid and Its More Potent Antiprotozoal Analogues
Betulinic acid (BA, 3β-hydroxy-lup-20(29)-en-28-oic acid) is a pentacyclic triterpene acid present predominantly in <i>Betula</i> ssp. (Betulaceae) and is also widely spread in many species belonging to different plant families. BA presents a wide spectrum of remarkable pharmacological p...
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MDPI AG
2021-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/4/1081 |
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| author | André Barreto Cunha Ronan Batista María Ángeles Castro Jorge Mauricio David |
| author_facet | André Barreto Cunha Ronan Batista María Ángeles Castro Jorge Mauricio David |
| author_sort | André Barreto Cunha |
| collection | DOAJ |
| description | Betulinic acid (BA, 3β-hydroxy-lup-20(29)-en-28-oic acid) is a pentacyclic triterpene acid present predominantly in <i>Betula</i> ssp. (Betulaceae) and is also widely spread in many species belonging to different plant families. BA presents a wide spectrum of remarkable pharmacological properties, such as cytotoxic, anti-HIV, anti-inflammatory, antidiabetic and antimicrobial activities, including antiprotozoal effects. The present review first describes the sources of BA and discusses the chemical strategies to produce this molecule starting from betulin, its natural precursor. Next, the antiprotozoal properties of BA are briefly discussed and the chemical strategies for the synthesis of analogues displaying antiplasmodial, antileishmanial and antitrypanosomal activities are systematically presented. The antiplasmodial activity described for BA was moderate, nevertheless, some C-3 position acylated analogues showed an improvement of this activity and the hybrid models—with artesunic acid—showed the most interesting properties. Some analogues also presented more intense antileishmanial activities compared with BA, and, in addition to these, heterocycles fused to C-2/C-3 positions and amide derivatives were the most promising analogues. Regarding the antitrypanosomal activity, some interesting antitrypanosomal derivatives were prepared by amide formation at the C-28 carboxylic group of the lupane skeleton. Considering that BA can be produced either by isolation of different plant extracts or by chemical transformation of betulin, easily obtained from <i>Betula</i> ssp., it could be said that BA is a molecule of great interest as a starting material for the synthesis of novel antiprotozoal agents. |
| first_indexed | 2024-03-09T00:44:56Z |
| format | Article |
| id | doaj.art-a9115d19df7b4579b8024d8f7e0d9709 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T00:44:56Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a9115d19df7b4579b8024d8f7e0d97092023-12-11T17:33:55ZengMDPI AGMolecules1420-30492021-02-01264108110.3390/molecules26041081Chemical Strategies towards the Synthesis of Betulinic Acid and Its More Potent Antiprotozoal AnaloguesAndré Barreto Cunha0Ronan Batista1María Ángeles Castro2Jorge Mauricio David3Instituto de Química, Universidade Federal da Bahia, Salvador 40170-280, BA, BrazilInstituto de Química, Universidade Federal da Bahia, Salvador 40170-280, BA, BrazilDepartment of Pharmaceutical Sciences, Pharmaceutical Chemistry Section, CIETUS/IBSAL, Faculty of Pharmacy, University of Salamanca, 37007 Salamanca, SpainInstituto de Química, Universidade Federal da Bahia, Salvador 40170-280, BA, BrazilBetulinic acid (BA, 3β-hydroxy-lup-20(29)-en-28-oic acid) is a pentacyclic triterpene acid present predominantly in <i>Betula</i> ssp. (Betulaceae) and is also widely spread in many species belonging to different plant families. BA presents a wide spectrum of remarkable pharmacological properties, such as cytotoxic, anti-HIV, anti-inflammatory, antidiabetic and antimicrobial activities, including antiprotozoal effects. The present review first describes the sources of BA and discusses the chemical strategies to produce this molecule starting from betulin, its natural precursor. Next, the antiprotozoal properties of BA are briefly discussed and the chemical strategies for the synthesis of analogues displaying antiplasmodial, antileishmanial and antitrypanosomal activities are systematically presented. The antiplasmodial activity described for BA was moderate, nevertheless, some C-3 position acylated analogues showed an improvement of this activity and the hybrid models—with artesunic acid—showed the most interesting properties. Some analogues also presented more intense antileishmanial activities compared with BA, and, in addition to these, heterocycles fused to C-2/C-3 positions and amide derivatives were the most promising analogues. Regarding the antitrypanosomal activity, some interesting antitrypanosomal derivatives were prepared by amide formation at the C-28 carboxylic group of the lupane skeleton. Considering that BA can be produced either by isolation of different plant extracts or by chemical transformation of betulin, easily obtained from <i>Betula</i> ssp., it could be said that BA is a molecule of great interest as a starting material for the synthesis of novel antiprotozoal agents.https://www.mdpi.com/1420-3049/26/4/1081betulinic acidantiprotozoal activitiestriterpene acid derivativesantiplasmodial activityantileishmanial activityantitrypanosomal activity |
| spellingShingle | André Barreto Cunha Ronan Batista María Ángeles Castro Jorge Mauricio David Chemical Strategies towards the Synthesis of Betulinic Acid and Its More Potent Antiprotozoal Analogues Molecules betulinic acid antiprotozoal activities triterpene acid derivatives antiplasmodial activity antileishmanial activity antitrypanosomal activity |
| title | Chemical Strategies towards the Synthesis of Betulinic Acid and Its More Potent Antiprotozoal Analogues |
| title_full | Chemical Strategies towards the Synthesis of Betulinic Acid and Its More Potent Antiprotozoal Analogues |
| title_fullStr | Chemical Strategies towards the Synthesis of Betulinic Acid and Its More Potent Antiprotozoal Analogues |
| title_full_unstemmed | Chemical Strategies towards the Synthesis of Betulinic Acid and Its More Potent Antiprotozoal Analogues |
| title_short | Chemical Strategies towards the Synthesis of Betulinic Acid and Its More Potent Antiprotozoal Analogues |
| title_sort | chemical strategies towards the synthesis of betulinic acid and its more potent antiprotozoal analogues |
| topic | betulinic acid antiprotozoal activities triterpene acid derivatives antiplasmodial activity antileishmanial activity antitrypanosomal activity |
| url | https://www.mdpi.com/1420-3049/26/4/1081 |
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