Synthesis and Antiplasmodial Activity of Betulinic Acid and Ursolic Acid Analogues

More than 40% of the World population is at risk of contracting malaria, which affects primarily poor populations in tropical and subtropical areas. Antimalarial pharmacotherapy has utilised plant-derived products such as quinine and artemisinin as well as their derivatives. However, worldwide use of these antimalarials has caused the spread of resistant parasites, resulting in increased malaria morbidity and mortality. Considering that the literature has demonstrated the antimalarial potential of triterpenes, specially betulinic acid (1) and ursolic acid (2), this study investigated the antimalarial activity against P. falciparum chloroquine-sensitive 3D7 strain of some new derivatives of 1 and 2 with modifications at C-3 and C-28. The antiplasmodial study employed flow cytometry and spectrofluorimetric analyses using YOYO-1, dihydroethidium and Fluo4/AM for staining. Among the six analogues obtained, compounds 1c and 2c showed excellent activity (IC50 = 220 and 175 nM, respectively) while 1a and b demonstrated good activity ( IC50 = 4 and 5 mu M, respectively). After cytotoxicity evaluation against HEK293T cells, 1a was not toxic, while 1c and 2c showed IC50 of 4 mu M and a selectivity index (SI) value of 18 and 23, respectively. Moreover, compound 2c, which presents the best antiplasmodial activity, is involved in the calcium-regulated pathway(s).Instituto Nacional de Ciencia e Tecnologia para Inovacao Farmaceutica (INCTif, Brazil)Instituto Nacional de Ciencia e Tecnologia para Inovacao Farmaceutica (INCT-if, Brazil)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), BrazilConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq-Brazil)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), BrazilCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES-Brazil)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), BrazilFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Brazil)Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS, Brazil)Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS, Brazil)FAPESPFAPES

Derivados oleananos e ursanos e sua importância na descoberta de novos fármacos com atividade antitumoral, anti-inflamatória e antioxidante Oleanane and ursane derivatives and their importance on the discovery of potential antitumour, antiinflammatory and antioxidant drugs

<abstract language="eng">Oleanolic and ursolic acids are triterpenes that exist abundantly in the plant kingdom. They show antitumor activity and their cytotoxic activity was already evaluated against a broad range of cell lines. The inhibition of enzymes involved in the metabolism of DNA and the induction of apoptosis are known events that have been related to the antitumour activity of these triterpenes. The antiinflamatory and antioxidant activities also seem to play an important role in their antitumour activity. In this review, it is presented an overview of the importance of the potential antitumour, antiinflamatory and antioxidant activities of these triterpenoid derivatives. Also, we propose a structural-activity relationship to triterpenes containing oleanane or ursane skeleton and their cytotoxic activity

Triterpenes and saponins from Ilex argentina leaves

Ilex argentina es una de las especies que ha sido mencionada como adulterante o sustituto de la yerba mate verdadera (l. paraguariensis). De las hojas fueron aisladas dos saponinas y un triterteno y sus estructuras químicas elucidadas a través de métodos espectroscópicos. El triterpeno fue identificado como el ácido rotúndico y las saponitias como el éster 28-0-Β-D-glucopiranósido del ácido rotúndico(pedunculósido)y el isómero 20(S) del éster 28-O-Β-D-glucopiranósido del ácido rotundioico.From Ilex argentina Lillo leaves, a species reported as substitute or adulterant of the genuine erva-maté (Ilex paraguariensis A. St.-Hil.), two saponins and one triterpene have been isolated. By means of spectroscopic methods, this latter was identified as rotundic acid and the saponins as the 28-0-Β-D-glucopyranosylester of rotundic acid (pedunculoside)and the 20(S) isomer of 28-O-Β-D-glucopyranosylester of rotundioic acid.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Triterpenes and saponins from Ilex argentina leaves

Ilex argentina es una de las especies que ha sido mencionada como adulterante o sustituto de la yerba mate verdadera (l. paraguariensis). De las hojas fueron aisladas dos saponinas y un triterteno y sus estructuras químicas elucidadas a través de métodos espectroscópicos. El triterpeno fue identificado como el ácido rotúndico y las saponitias como el éster 28-0-Β-D-glucopiranósido del ácido rotúndico(pedunculósido)y el isómero 20(S) del éster 28-O-Β-D-glucopiranósido del ácido rotundioico.From Ilex argentina Lillo leaves, a species reported as substitute or adulterant of the genuine erva-maté (Ilex paraguariensis A. St.-Hil.), two saponins and one triterpene have been isolated. By means of spectroscopic methods, this latter was identified as rotundic acid and the saponins as the 28-0-Β-D-glucopyranosylester of rotundic acid (pedunculoside)and the 20(S) isomer of 28-O-Β-D-glucopyranosylester of rotundioic acid.Colegio de Farmacéuticos de la Provincia de Buenos Aire

A highly active triterpene derivative capable of biofilm damage to control cryptococcus spp.

Cryptococcus neoformans is an encapsulated yeast responsible for more than 180,000 deaths per year. The standard therapeutic approach against cryptococcosis is a combination of amphotericin B with flucytosine. In countries where cryptococcosis is most prevalent, 5-fluorocytosine is rarely available, and amphotericin B requires intravenous administration. C. neoformans biofilm formation is related to increased drug resistance, which is an important outcome for hospitalized patients. Here, we describe new molecules with anti-cryptococcal activity. A collection of 66 semisynthetic derivatives of ursolic acid and betulinic acid was tested against mature biofilms of C. neoformans at 25 mu M. Out of these, eight derivatives including terpenes, benzazoles, flavonoids, and quinolines were able to cause damage and eradicate mature biofilms. Four terpene compounds demonstrated significative growth inhibition of C. neoformans. Our study identified a pentacyclic triterpenoid derived from betulinic acid (LAFIS13) as a potential drug for anti-cryptococcal treatment. This compound appears to be highly active with low toxicity at minimal inhibitory concentration and capable of biofilm eradication912CAPES - Coordenação de Aperfeiçoamento de Pessoal e Nível SuperiorFAPESP – Fundação de Amparo à Pesquisa Do Estado De São PauloSem informação420276/2016-5; 302637/2017-6; 307191/2016-

The Inhibitory Effects of Phenolic and Terpenoid Compounds from Baccharis trimera in Siha Cells: Differences in Their Activity and Mechanism of Action

Baccharis trimera is used in folk medicine as a tea for digestive and liver diseases. It possesses anti-inflammatory and antioxidant properties that are related to the presence of phenolic compounds. The aim of this work was to investigate the anti-proliferative properties of phenolic (PHE) and terpenoid (SAP) compounds from B. trimera on human cervical cancer. The treatment of SiHa cells with PHE for 24 h suppressed colony formation in a dose-dependent manner, inhibited proliferation and inhibited cell motility. Although SAP inhibited the proliferation of SiHa cells in a dose-dependent manner, it increased colony formation and did not inhibit cell motility. PHE and SAP also promoted a significant increase in lactate dehydrogenase levels in the culture medium in a dose-dependent manner, indicating a loss of cell membrane integrity. Moreover, PHE promoted necrotic cell death, whereas SAP induced apoptosis. These compounds are new anticancer prototypes due their significant anticancer activity demonstrated herein

Syntheis and in vivo assay of indometacin esters as a Medicinal Chemistry practical class for graduate students

This article shows a Medicinal Chemistry practical class, created and developed by students of the Pharmaceutical Sciences Post-Graduate Program (PPGCF/UFRGS). It describes the planning, synthesis and in vivo biological evaluation of four ester derivatives of the non-steroidal anti-inflammatory drug Indomethacin (IndOH) as a proposal for practical classes of Medicinal Chemistry.Este artigo apresenta uma aula prática de Química Medicinal, criada e desenvolvida por estudantes do Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF/UFRGS). Descreve o planejamento, síntese e avaliação biológica de quatro ésteres derivados do fármaco anti-inflamatório não-esteróide Indometacina (IndOH) como aula prática para alunos de Química Medicinal.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Phenolic Enriched Extract of Baccharis trimera Presents Anti-inflammatory and Antioxidant Activities

Baccharis trimera is a plant popularly used as a tea and to treat gastrointestinal diseases and inflammatory processes as well. The total phenolic content was determined and the antioxidant and anti-inflammatory activities of six extracts (dichloromethane, ethyl acetate, butanol, aqueous, saponin and phenolic) from B. trimera were evaluated. Using carrageenan-induced pleurisy as a model of acute inflammation, the phenolic extract at 15 mg/kg decreased significantly the analyzed parameters when compared to the carrageenan group ( p < 0.05), thus showing potential anti-inflammatory activity. The total phenolic content and antioxidant activity were evaluated by the Folin-Ciocalteau and DPPH methods, respectively. Phenolic and ethyl acetate extracts presented higher antioxidant activity ( p < 0.05) than ascorbic acid. The phenolic extract also showed the highest antioxidant potential in relation to the other extracts, thus suggesting that the antioxidant and anti-inflammatory activities were due to the presence of phenolic compounds