Maria Lucilia dos Santos

Cytotoxic profile of natural and some modified bufadienolides from toad Rhinella schneideri parotoid gland secretion

Cutaneous secretions of toad species are an important source of bufadienolides, compounds that exhibit interesting structural features and biopharmacological properties. Here we describe the isolation of bufadienolides from the Brazilian toad Rhinella schneideri parotoid glands secretion, including: marinobufagin (1), bufalin (2), telocinobufagin (3), hellebrigenin (4), and the atypical 20S,21R-epoxymarinobufagin (5) besides the widespread beta-sitosterol (6). Starting from natural bufadienolides four derivatives were prepared: 3beta-acetoxy-marinobufagin (7), 3beta-acetoxy-bufalin (8), 3beta-acetoxy-telocinobufagin (9), and 3beta-acetoxy-20S,21R-epoxymarinobufagin (10). The cytotoxic evaluation showed that all natural bufadienolides and their derivatives exhibited moderate to strong activity against human HL-60, SF-295, MDA-MB-435, and HCT-8 cancer cell strains without hemolysis of mouse erythrocytes. The acetylated bufadienolides (7-9) and the epoxide 10 showed lesser peripheral blood lymphocytes (PBLs) inhibitory activity than their precursors, suggesting that chemical modifications on such compounds can play an important role on the modulation of their cytotoxic profile.

Utilisation of Cashew Nut Shell Liquid from Anacardium occidentale as Starting Material for Organic Synthesis: A Novel Route to Lasiodiplodin from Cardols

As part of an ongoing program concerning utilisation of CNSL (Cashew Nut Shell Liquid) from Anacardium occidentale as starting material for the preparation of useful compounds, we describe the conversion of cardols (6-alkenylresorcinols) into lasiodiplodin, a naturally occurring 12-membered orsellinic acid type macrolide, which exhibits plant growth regulating and antileukemic properties.

Synthesis and cytotoxicity screening of substituted isobenzofuranones designed from anacardic acids.

This work is part of a large program, which seeks to discover new antitumor isobenfuranones designed from anacardic acids. The synthetic strategy for the construction of the title compounds takes into consideration the use of inexpensive anacardic acids (2), the major natural cashew (Anacardium occidentale) nut-shell phenolic lipid, and features one-pot construction of fused-ring aromatic gamma-lactones, phthalides. The cytotoxicity screening in different human cancer cell lines (HL-60 leukemia, SF295 glioblastoma and MDA-MB435 melanoma) by the MTT assay showed that acyclic precursor (6), and isobenfuranones (1a and 1b) are active compounds. Interestingly, 1a exhibits significant antiproliferative effect against HL-60 cells and moderate activity against SF295 and MDA-MB435 cell lines. Analysis of mechanisms involved in the cytotoxic activity showed that active compounds were leading to DNA damage, triggering apoptosis or necrosis induction.

Synthesis and biological evaluation of new salicylate macrolactones from anacardic acids

In connection with our ongoing investigation in the search for new bioactive compounds using non-isoprenoid phenolic lipids from Anacardium occidentale as starting material, we describe the synthesis and cytotoxicity screening of some novel salicylate macrolactones prepared from anacardic acids, the major constitutents of natural cashew nut-shell liquid (CNSL).

Inhibitory effect of combinations of digoxin and endogenous cardiotonic steroids on Na+/K+-ATPase activity in human kidney membrane preparation

AIMS Cardiac glycosides have been extensively used in the treatment of congestive heart failure for more than 200 years. Recently, cardenolides and bufadienolides were isolated from mammalian tissue and are considered as a new class of steroidal hormones. The aim of the present work was to characterize the interaction between the most clinical used cardiac glycoside digoxin and the cardiac glycosides known to exist endogenously, i.e., ouabain, marinobufagin and telocinobufagin, on human kidney Na(+)/K(+)-ATPase. MAIN METHODS Inhibition of Na(+)/K(+)-ATPase activity from crude membrane preparations of human kidney was performed using increasing concentrations of the drugs alone or mixtures of ouabain:digoxin, telocinobufagin:digoxin and marinobufagin:digoxin in a fixed ratio 1:4, 2:3 and 3:2, respectively. The colorimetric method of Fiske and Subbarow was used to measure the inorganic phosphate released. KEY FINDINGS Analyses of inhibition curves showed that the experimental curves for all combinations were superimposed on the theoretical additive curves indicating that an additive effect occurs among distinct cardenolides and bufadienolides combinations on the human α1β1 Na(+)/K(+)-ATPase protomer. SIGNIFICANCE Considering the extensive use of digoxin in the treatment of heart failure and the recent findings that endogenous cardiac glycosides may have altered levels in many diseases, including heart failure, the demonstration of additive effect between cardiac glycosides can help in the understanding of recent clinical observations, including that lower than usual doses of cardiac glycosides are necessary for decreasing mortality in these patients.

Characterization and biological properties of Pouteria torta extracts: a preliminary study

Hexane, ethanol and aqueous extracts and fractions from leaves of Pouteria torta (Mart.) Radlk (Sapotaceae), a perennial tree, widespread in the Brazilian Cerrado, were tested for cytotoxicity with the Artemia salina toxicity model. Only the aqueous crude extract and the MeCN:CHCl3 fraction of the ethanol extract presented toxicity (0.28 mg/mL and 0.27mg/mL, respectively). Lupeol acetate was isolated from the hexane extract. It is the first report of lupeol acetate from the genus Pouteria.

New application of triphosgene in a convenient synthesis of 3-aryl-1,3-benzoxazine-2,4-diones from anacardic acids

In conjunction with a search program focused on utilization of cashew (Anacardium occidentale) nut shell liquid (CNSL) as starting material for the preparation of useful compounds, a convenient synthesis of novel series of 3-aryl-1,3-benzoxazine-2,4-diones was prepared from anacardic acids by using of the triphosgene.

Synthesis of 2-Hydroxy-3-methyl-2-cyclo-pentenone, Corylone, from 2-Ketoglutaric Acid

Abstract Treatment of 2-ketoglutaric acid with diazomethane gave 2-(metoxycarbonyl)-oxiranepropanoic acid methyl ester (2) wich lead to 2-hydroxy-2-methyl-glutaric acid dimethyl ester (3) by catalytic hydrogenation, wich was further processed to the title compound.

Characterization of cytotoxic activity of compounds derived from anacardic acid, cardanol and cardol in oral squamous cell carcinoma

Background Cancer is the second leading cause of death worldwide, and oral cancer ranks tenth among all types [1]. Chemotherapy, radiotherapy and surgery are current therapeutic options; however these are not fully efficient. Permanent functional impairment and aesthetic scars are frequent [2]. In this scenario, it is crucial to find therapeutic alternatives, including those derived from the flora, which currently provides about 1/3 of all new medicines. Anacardic acids, cardanols and cardols are the main constituents of the cashew nut shell liquid (herein referred to as “LCC”) and together, account for 90% of its composition. The liquid is an industrial byproduct, with low economic value prior to processing. The nut, the proper fruit from the plant Anacardium occidentale, is edible. Anacardic acids, cardols and cardanols are made of a phenolic ring connected to a long side chain (usually C15H31-n) that can bear several to none insaturations. Additionally, a methyl group can be found in the phenolic ring [3]. Apart from current industrial uses, it has been demonstrated that some of these compounds may exert microbicide and antioxidative activities. Anacardic acid has been shown to be cytotoxic to lung, liver and gastric tumor cells through epigenetic mechanisms by inhibiting histone acetyltransferases (HATs) [4] and in a capase-independent manner [5]. However, given the possible molecular diversity obtained from LCC constituents, not all distinct LCC derivatives have yet been fully analyzed or characterized. Aim The aim of the present study was to screen for compounds with cytotoxic activity in oral cancer cells and characterize the observed effect.

Influence of the rainfall regime on the mobility of zn, cd, ni, cu, mn and fe in the surface sediments of the contas river located in the Brazilian semi-arid region

In this study, the influences of the rainfall regimes and of the land use in the mobility of Zn, Cd, Ni, Cu, Mn and Fe in the surface sediment of the Contas River (Bahia State, Brazil) was evaluated with basis on the fractionation method that uses a three-step sequential extraction. The study was conducted in the middle of the Contas River, in an area that encompasses the urban perimeter and part of the rural zone of Jequie City that is influenced by agricultural, urban and industrial activities. The determinations of metals were conducted by flame atomic absorption spectrometry (FAAS). The result obtained from this study indicates that the concentrations of the metals in the soluble fractions of the sediments are directly associated with rainfall indices in the region. The study also indicated that the metals Zn, Cu, Cd and Ni exhibit higher concentrations in the sediments within the city.