Metabolites from roots of Colubrina greggii var. yucatanensis and evaluation of their antiprotozoan, cytotoxic and antiproliferative activities

Abstract

A purificação do extrato da raiz de Colubrina greggii var. yucatanensis levou ao isolamento e identificação do ácido 3-O-acetil ceanótico, um novo triterpeno natural, juntamente com os metabólitos já descritos: ácido ceanótico, ácido cenoténico, ácido betulínico, discarina B e crisofaneína. Os produtos naturais e os derivados semi-sintéticos éster de acetil dimetil ceanotato, dimetil ceanotato e peracetato de crisofaneína mostraram moderada a baixa atividade leishmanicida e tripanocida. Nenhum dos metabólitos mostrou ser citotóxicos ou ter atividade antiproliferativa. Os resultados também sugerem que o ácido betulínico contribui para a atividade antiplasmódica inicialmente detectada na raiz do extrato bruto de C. greggii var. yucatanensis.Purification of the root extract of Colubrina greggii var. yucatanensis resulted in the isolation and identification of 3-O-acetyl ceanothic acid as a new natural ceanothane triterpene, together with the known metabolites ceanothic acid, cenothenic acid, betulinic acid, discarine B and chrysophanein. The natural products and the semisynthetic esters acetyl dimethyl ceanothate, dimethyl ceanothate and chrysophanein peracetate showed moderate to low leishmanicidal and trypanocidal activities. None of the metabolites showed cytotoxic or antiproliferative effects. The results also suggested that betulinic acid contributes to the antiplasmodial activity originally detected in the crude root extract of C. greggii var. yucatanensis. Keywords: Colubrina greggii var. yucatanensis, Rhamnaceae, antiprotozoan, cytotoxic ceanothane IntroductionLeishmaniosis, trypanosomiosis and malaria are a group of protozoan diseases considered of significant importance due to their incidence and rate of mortality in developing countries. 1 The low effectiveness, limited availability and high toxicity of existing treatments for these illnesses emphasize the importance of continuing the search for new antiprotozoan pharmaceuticals.2 Plants are considered an important source of biologically active natural products, 3 including a number of them with antiprotozoan activity. [4][5][6] During the screening of extracts from native Yucatecan medicinal plants as potential sources of bioactive metabolites, the root extract of Colubrina greggii S. Watson var. yucatanensis M. C. Johnst., a shrub used for the treatment of liver diseases, ulcerations, abscesses, asthma and tuberculosis, 7 showedMetabolites from Roots of Colubrina greggii var. yucatanensis J. Braz. Chem. Soc. 1280 trypanocidal, antimalarial, leishmanicidal and cytostatic activity. 8,9 Previous phytochemical studies of the genus Colubrina (Rhamnaceae), which include 31 species, 10 reported the presence of a wide structural diversity of metabolites, including ansa macrolides, saponins, aporphinic alkaloids, phenolic acids, flavones and triterpenoid acids. 11-18To date, only chrysophanol, an anthraquinone with antimicrobial activity, has been reported as a metabolite from C. greggii. 19 In the present study we report the leishmanicidal, trypanocidal, a...

Natural Products from the Yucatecan Flora: Structural Diversity and Biological Activity

“…(Rhamnaceae), a shrub used for the treatment of liver diseases, ulcerations, and tuberculosis in Mayan traditional medicine. 62 The natural ceanothanes and some synthetic derivatives showed moderate leishmanicidal and trypanocidal activities when tested against Leishmania amazonensis and Trypanosoma cruzi var. tulahuen, respectively.…”

“…tulahuen. 62 A different class of metabolites, the benzochromenes (6,6dimethyl-2-methoxy-6H-benzo[c]chromen-9-yl)methanol (108) and 2-methoxy-6,6-dimethyl-6H-benzo[c]chromen-9carbaldehyde (109), isolated from the root extract of Bourreria pulchra Millsp. (Boraginaceae), a medicinal plant with DNAinteracting activity, also exhibited antiprotozoal properties, with 108 being particularly active against L. mexicana and T. cruzi.…”

“…A phytochemical investigation of the root extract of C. greggi yielded two bioactive metabolites identified as the athraquinone chrysophanol ( 106 ), active against Bacillus subtilis and Staphylococcus aureus , and discarine B ( 107 ), a cyclic dipeptide with moderate antiprotozoal activity against T. cruzi var. tulahuen …”

Preparation of Derivatives of Betulinic Acid, Steviol and Isosteviol and Evaluation of Antitrypanosomal and Antimalarial Activities

“…6 Other studies have also reported the antimalarial potential of that compound and its derivatives. [7][8][9][10][11][12][13][14][15][16][17][18][19][20] A few tetracyclic diterpenes have also shown antimalarial properties. One example is a norpimaran lactone (1d, Figure 1) obtained from manool, 21 and another is kaurenoic acid (3a, Figure 3) described as weakly active.…”