Semisynthesis, cytotoxicity, antimalarial evaluation and structure-activity relationship of two series of triterpene derivatives

Cargnin, Simone Tasca; Staudt, Andressa Finkler; Medeiros, Patrícia de Maria de Soares; Sol, Daniel de Medeiros Sol; Santos, Ana Paula de Azevedo dos; Zanchi, Fernando Berton; Gosmann, Grace; Puyet, Antonio; Teles, Carolina Bioni Garcia; Gnoatto, Simone Cristina Baggio

doi:10.1016/j.bmcl.2017.12.060

Cited by 16 publications

(13 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pentacyclic triterpenes have been already reported to show promising antimalarial potential (Beaufay et al 2018; Isah et al 2016) and some of them display high antiplasmodial activity and low cytotoxicity alone, in mixtures or in combination with artemisinin (Cargnin et al 2018; Da Silva et al 2013; Ma et al 2008; Phillipson and O’Neill 1987). They also possess various pharmacological effects and are thought to act as multi-target compounds (Moneriz et al 2011).…”

Section: Resultsmentioning

confidence: 99%

“…The need to discover new prototypes of drugs is thus very important. In this context, natural products provide a high degree of lead-/drug-similarity, remaining undoubtedly the best source of native drugs or structural templates for antimalarial compounds development (Cargnin et al 2018; Da Silva et al 2013). A recent review reporting the new drugs available on the market during the last 34 years showed that approximately 60% of these new antiparasitic drugs have a natural origin/pharmacophore (Newman and Cragg 2016).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of antiplasmodial triterpenes from Keetia species using NMR-based metabolic profiling

et al. 2019

View full text Add to dashboard Cite

Introduction The increase in multidrug resistance and lack of efficacy in malaria therapy has propelled the urgent discovery of new antiplasmodial drugs, reviving the screening of secondary metabolites from traditional medicine. In plant metabolomics, NMR-based strategies are considered a golden method providing both a holistic view of the chemical profiles and a correlation between the metabolome and bioactivity, becoming a corner stone of drug development from natural products. Objective Create a multivariate model to identify antiplasmodial metabolites from 1 H NMR data of two African medicinal plants, Keetia leucantha and K. venosa . Methods The extracts of twigs and leaves of Keetia species were measured by 1 H NMR and the spectra were submitted to orthogonal partial least squares (OPLS) for antiplasmodial correlation. Results Unsupervised 1 H NMR analysis showed that the effect of tissues was higher than species and that triterpenoids signals were more associated to Keetia twigs than leaves. OPLS–DA based on Keetia species correlated triterpene signals to K. leucantha , exhibiting a higher concentration of triterpenoids and phenylpropanoid-conjugated triterpenes than K. venosa . In vitro antiplasmodial correlation by OPLS, validated for all Keetia samples, revealed that phenylpropanoid-conjugated triterpenes were highly correlated to the bioactivity, while the acyclic squalene was found as the major metabolite in low bioactivity samples. Conclusion NMR-based metabolomics combined with supervised multivariate data analysis is a powerful strategy for the identification of bioactive metabolites in plant extracts. Moreover, combination of statistical total correlation spectroscopy with 2D NMR allowed a detailed analysis of different triterpenes, overcoming the challenge posed by their structure similarity and coalescence in the aliphatic region. Electronic supplementary material The online version of this article (10.1007/s11306-019-1487-4) contains supplementary material, which is available to authorized users.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of antiplasmodial triterpenes from Keetia species using NMR-based metabolic profiling

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Subsequently, the compounds were characterized by spectroscopic techniques such as infrared and nuclear magnetic resonance. Our group (Cargnin et al., 2018) previously described all the methods and the spectroscopic characterization.…”

Section: Methodsmentioning

confidence: 99%

Ursolic and betulinic semisynthetic derivatives show activity against CQ‐resistant Plasmodium falciparum isolated from Amazonia

et al. 2021

View full text Add to dashboard Cite

ACT’s low levels of Plasmodium parasitemia clearance are worrisome since it is the last treatment option against P. falciparum. This scenario has led to investigations of compounds with different mechanisms of action for malaria treatment. Natural compounds like ursolic acid (UA) and betulinic acid (BA), distinguished by their activity against numerous microorganisms, including P. falciparum, have become relevant. This study evaluated the antiplasmodial activity of imidazole derivatives of UA and BA against P. falciparum in vitro. Eight molecules were obtained by semisynthesis and tested against P. falciparum strains (NF54 and CQ‐resistant 106/cand isolated in Porto Velho, Brazil); 2a and 2b showed activity against NF54 and 106/cand strains with IC50 < 10 µM. They presented high selectivity indexes (SI > 25) and showed synergism when combined with artemisinin. 2b inhibited the parasite's ring and schizont forms regardless of when the treatment began. In silico analysis presented a tight bind of 2b in the topoisomerase II‐DNA complex. This study demonstrates the importance of natural derivate compounds as new candidates for malarial treatment with new mechanisms of action. Semisynthesis led to new triterpenes that are active against P. falciparum and may represent new alternatives for malaria drug development.

show abstract

“…In another study, the synthesis of a novel series of BA derivatives was performed by acetic, butyric and isobutyric esterification at the C-3 OH group, as well as by incorporating methoxy and imidazole moieties at the carboxyl at the C-28 position [ 54 ]. The antiplasmodial activities of all analogues were assessed against the chloroquine-resistant P. falciparum W2 strain.…”

Section: Synthesis Of Antiprotozoal Ba Analoguesmentioning

confidence: 99%

Chemical Strategies towards the Synthesis of Betulinic Acid and Its More Potent Antiprotozoal Analogues

et al. 2021

View full text Add to dashboard Cite

Betulinic acid (BA, 3β-hydroxy-lup-20(29)-en-28-oic acid) is a pentacyclic triterpene acid present predominantly in Betula 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 Betula ssp., it could be said that BA is a molecule of great interest as a starting material for the synthesis of novel antiprotozoal agents.

show abstract

Semisynthesis, cytotoxicity, antimalarial evaluation and structure-activity relationship of two series of triterpene derivatives

Cited by 16 publications

References 29 publications

Identification of antiplasmodial triterpenes from Keetia species using NMR-based metabolic profiling

Identification of antiplasmodial triterpenes from Keetia species using NMR-based metabolic profiling

Ursolic and betulinic semisynthetic derivatives show activity against CQ‐resistant Plasmodium falciparum isolated from Amazonia

Chemical Strategies towards the Synthesis of Betulinic Acid and Its More Potent Antiprotozoal Analogues

Contact Info

Product

Resources

About