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Narcissus L. is a renowned plant genus with a notable center of diversity and is primarily located in the Mediterranean region. These plants are widely recognized for their ornamental value, owing to the beauty of their flowers; nonetheless, they also hold pharmacological importance. In Europe, pharmaceutical companies usually use the bulbs of Narcissus pseudonarcissus cv. Carlton to extract galanthamine, which is one of the few medications approved by the FDA for the palliative treatment of mild-to-moderate symptoms of Alzheimer's disease. The purpose of this study was to evaluate the potential of these plants in Alzheimer's disease. The alkaloid extract from the leaves of different species of Narcissus was obtained by an acid-base extraction work-up -procedure. The biological potential of the samples was carried out by evaluating their ability to inhibit the enzymes acetyl- and butyrylcholinesterase (AChE and BuChE, respectively). The species N. jacetanus exhibited the best inhibition values against AChE, with IC 50 values of 0.75 ± 0.03 µg·mL -1 , while N. jonquilla was the most active against BuChE, with IC 50 values of 11.72 ± 1.15 µg·mL -1 .

This study aimed to evaluate the in silico and in vitro inhibitory effect of the combined use of galantamine (GAL) and donepezil (DON) against acetylcholinesterase and butyrylcholinesterase (BuChE) enzymes. In silico and in vitro cholinesterase analysis were carried out for GAL and DON alone and combined. Molecular modeling studies were carried out (docking analysis, molecular dynamics simulation, and quantum theory of atoms in molecules). Cholinesterase's inhibitory activities by modified Ellman's method and the drug combination effect using the Chou-Talalay method were assayed. GAL/DON combination showed the co-occupancy of the ligands in both enzymes through in silico studies. Regarding in vitro BuChE inhibition analyses, three of five combinations showed an interaction between GAL and DON at the threshold of additive affect (0.9 < CI < 1.1), with a tendency toward a synergistic effect for higher concentrations. This is the first report showing the efficacy of the GAL/DON combinations inhibiting BuChE, showing the importance of analyzing the behavior of different ligands when co-occupancy into the active site is possible. These combinations might be a possible therapy to improved efficacy, reduced doses, minor side effects, and high levels of the neurotransmitter in the synaptic space for Alzheimer's disease., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

This study highlights Adesmia pinifolia , a native high-Andean species, as a potential candidate for the phytoremediation of soils contaminated with Cd and Hg. In this work, a semi-hydronic assay with different doses of Cd (3, 4.5, and 6 mg L -1 ) and Hg (0.8, 1.2, and 1.6 mg L -1 ) was analysed to evaluate the establishment of plants, antioxidant defence systems, oxidative stress, and the ability to accumulate heavy metals. The results indicate high survival rates (>80%); however, Cd significantly reduced shoot and root biomass, while Hg increased root biomass with the 1.6 mg L -1 treatment. Cd and Hg tend to accumulate more in roots (2534.24 µg/g and 596.4 µg g -1 , respectively) compared to shoots (398.53 µg g -1 and 140.8 µg g -1 , respectively). A significant decrease in the bioconcentration factor of Cd and Hg in roots was observed as metal levels increased, reaching the maximum value at 3 mg L -1 (805.59 ± 54.38) and 0.8 mg L -1 (804.54 ± 38.09). The translocation factor, <1 for both metals, suggests that translocation from roots to shoots is limited. An overproduction of reactive oxygen species (ROS) was observed, causing lipid peroxidation and oxidative damage to plant membranes. Tolerance strategies against subsequent toxicity indicate that enhanced glutathione reductase (GR) activity and glutathione (GSH) accumulation modulate Cd and Hg accumulation, toxicity, and tolerance.

Microbial contamination remains a significant economic challenge in the food industry, emphasizing the need for innovative antimicrobial solutions. In this study, we synthesized N-sulfonyl-1,2,3,4-tetrahydroisoquinolines (NSTHIQ) derivatives using an environmentally friendly Preyssler heteropolyacid catalyst, obtaining moderate to high yields (35-91 %) under mild conditions. Two derivatives (5 and 6) exhibited significant antifungal properties against various fungal species, including Aspergillus spp, Penicillium spp, and Botrytis cinerea. ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis revealed the absence of hepatic toxicity in all compounds, making derivatives 2, 3, 4, and 5 potential candidates for further development. However, derivatives 6 and 7 exhibited immunotoxicity. In support of our experimental findings, reactivity indices were computed using Density Functional Theory principles, deriving valuable insights into the chemical properties of these derivatives. This study underscores the potential of NSTHIQ compounds as potent antifungal agents, coupled with the importance of employing environmentally friendly catalysts in drug discovery., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Chagas disease (CD), caused by Trypanosoma cruzi, represents a health threat to around 20 million people worldwide. Side effects of benznidazole (Bzn) cause 15-20% of patients to discontinue their treatment. Evidence has increased in favor of the use of drug combinations to improve the efficacy and tolerance of the treatment. Natural products are well known to provide structures that could serve as new drugs or scaffolds for CD treatment. Spp of the Amaryllidoideae sub family of Amaryllidaceae family are known by their bioactives alkaloids, which have been reported by their antiparasitic activities., Purpose: To evaluate the anti-T. cruzi activity of the isolated alkaloid candimine (Cnd) from Hippeastrum escoipense Slanis & Huaylla; and to assess the combination effect between Cnd and Bzn against different life stages of T. cruzi parasites., Methods: The chemical profile of H. escoipense alkaloids extract (AE-H. escoipense), including quantitation of Cnd was performed through GC/MS and UPLC-MS/MS techniques. Subsequently, Cnd was isolated using Shephadex LH-20. Then, the AE-H. escoipense and Cnd were tested against T. cruzi, (epimastigotes, trypomastigotes, and amastigotes) by in vitro proliferation and viability assays. The cytotoxicity was evaluated against Vero and HepG2 mammalian cells. The ultrastructural analysis was perform by transmission electron microscopy (TEM) and mitochondrial activity was carried out by MTT assay. Drug combination assay between Cnd and Bzn was evaluated using the Chou-Talalay method., Results: The AE-H. escoipense and Cnd showed high and specific anti-T. cruzi activity, comparable to Bzn. Cnd induces ultrastructural changes in T. cruzi, such as vacuolization, membrane blebs, and increased mitochondrial activity. Regarding the interaction between Cnd and Bzn, it generates synergism in the combinations of 0.25×IC 50 in epimastigotes, 2×IC 50 in trypomastigotes+amastigotes, and 0.25, 2, and 4×IC 50 in amastigotes., Conclusion: The synergism between Cnd and Bzn indicates that the combination at the concentration of 4×IC 50 could be useful as an effective new therapy against CD in the chronic stage. Thus, Cnd isolated from the leaves of H. escoipense emerges as potential candidate for the development of a new drug for the treatment of CD., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2023. Published by Elsevier GmbH.)

Background: Hippeastrum species have a wide range of biological properties. In Argentina, this genus comprises ten widely distributed species., Purpose: To evaluate the antiparasitic and anticholinesterase activities and chemical profiles of seven Argentinean Hippeastrum species and determine the synergism between the major isolated alkaloid-montanine-and benznidazole in anti- Trypanosoma cruzi activity., Methods: The antiparasitic activity was evaluated through antiproliferative and viability assays against T. cruzi epimastigotes. Synergism assays were performed using the Chou-Talalay method. AChE and BuChE inhibitory activities were also assessed. The alkaloid composition was obtained using GC-MS analysis., Results: All extracts showed strong growth inhibition of T. cruzi epimastigote proliferation. The extracts from H. aglaiae , H. aulicum , and H. hybrid stand out for their potent and total growth inhibition, which was comparable to benznidazole. The H. reticulatum extract showed strong Acetylcholinesterase (AChE) inhibitory activities, while five species showed moderate Butyrylcholinesterase (BuChE) inhibition. Fifteen alkaloids were identified by means of GC-MS. Regarding the synergism assessment, the highest synergistic effect was obtained from the combination of montanine and benznidazole., Conclusion: Hippeastrum species bulb extracts from Argentina were shown to be a good source of antiparasitic alkaloids and cholinesterase inhibitors. The synergism between montanine and benznidazole emerges as a potential combination for future studies to treat Chagas disease.

Background: Chagas disease, caused by the parasite Trypanosoma cruzi, affects over six million people worldwide, mainly in Latin American countries. Currently available drugs have variable efficacy in the chronic phase and significant side effects, so there is an urgent need for safer chemotherapeutic treatments. Natural products provide privileged structures that could serve as templates for the synthesis of new drugs. Among them, Amaryllidaceae plants have proved to be a potential natural source of therapeutical agents due to their rich diversity in alkaloids., Purpose: To identify alkaloids with anti-T. cruzi activity from Habranthus brachyandrus (Baker) Sealy (Amaryllidaceae, subfamily Amaryllidoideae) collected in Argentina., Methods: An H. brachyandrus alkaloid extract was tested against T. cruzi, and its cytotoxicity profile was evaluated against two mammalian cell lines to ascertain its selectivity against the parasite and potential liver toxicity. It was also assessed by a stage-specific anti-amastigote assay and analysed by GC/MS to determine its alkaloid profile. The isolated alkaloids were also tested using the aforementioned assays., Results: The extract showed high and specific activity against T. cruzi. The alkaloids lycoramine, galanthindole, 8-O-demethylmaritidine, 8-O-demethylhomolycorine, nerinine, trisphaeridine, deoxytazettine, and tazettamide were identified by means of GC-MS. In addition, hippeastidine (also named aulicine), tazzetine, ismine, and 3-epimacronine were isolated. The alkaloid ismine was specifically active against the parasite and had low toxicity against HepG2 cells, but did not show anti-amastigote activity., Conclusion: The extract had specific anti-T. cruzi activity and the isolated alkaloid ismine was partially responsible of it. These results encourage further exploration of H. brachyandrus alkaloids in search of novel starting points for Chagas disease drug development., (Copyright © 2022. Published by Elsevier GmbH.)

Triadimefon (TDM) and cyproconazole (CPZ) are two triazoles widely used as fungicides. Several azoles were synthesised starting from commercial TDM and CPZ. The compounds were evaluated against phytopathogenic filamentous fungi, including Aspergillus fumigatus (AF), A. niger (AN), A. ustus (AU), A. japonicus (AJ), A. terreus (AT), Fusarium oxysporum and Botrytis cinerea isolated from grapevine in the province of San Juan, Argentina. Three of the synthesised compounds (1-(Biphenyl-4-yloxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one, 1; 2-(Biphenyl-4-yl)-3-cyclopropyl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, 3; 3-Cyclopropyl-2-(4'-fluorobiphenyl-4-yl)-1-(1H-1,2,4-triazol1-yl)butan-2-ol, 4) presented remarkable in vitro fungicidal properties, with better effects than TDM and CPZ on some of the target fungi. Cytotoxicity was assessed using human lung fibroblasts MRC5. Derivative 1, with IC 50 values of 389.4 µM, was less toxic towards MRC-5 human lung fibroblasts than commercial TDM (248.5 µM) and CPZ (267.4 µM). Docking analysis and molecular dynamics simulations suggest that the compounds present the same interaction in the binding pocket of the CYP51B enzyme and with the same amino acids as CPZ. The derivatives investigated could be considered broad-spectrum but with some selectivity towards imperfect fungi., (© 2022. The Author(s).)

A lot of diseases are characterized by an increased inflammatory response with an exacerbated production of free radicals. The anti-inflammatory effect of different compounds with antioxidant capacity, as polyphenols present in grape is well known. Therefore, the objective is to evaluate the anti-oxidant and anti-inflammatory activity of waste product of wine production.Six different non-toxic-marc-polar extracts from Malbec and Syrah grape varieties were obtained, their total phenol and flavonoid content were evaluated, and their antioxidant and anti-inflammatory activity were determined.High content of total phenols and flavonoids were found mainly in extracts obtained from Syrah (80.51 ± 16.63 g equivalent to gallic acid/100 g and 25.47 ± 3.33 g equivalent to quercetin/100 g). In addition, they had a high antioxidant effect (above 88.5% of ABTS inhibition by Syrah extracts). Finally, all extracts decreased the nitric oxide (NO) production, but this was more accented when extract from Syrah obtained by infusion was used, which decreased NO levels to baseline (4.46 µM).Taking together, our results show the potential pharmaceutical use of waste product of wine making to prevent or to treat diseases which inflammatory response is exacerbated.

Chronic high-fat diet consumption induces hypercholesterolemia. The effect of Tessaria absinthioides (Hook. & Arn.) DC. (Asteraceae) was studied on the levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and triglycerides, and on the expression of liver X receptors (LXRs) in a hypercholesterolemic model. Adult male rats received a normal diet (ND) or a high-fat diet (HFD; normal diet + bovine fat + cholesterol). After 14 days, rats received water (W) or a decoction of the aerial parts of T. absinthioides (Ta; 10% w / v ) for 2, 4, or 6 weeks. Four and six weeks of Ta improved the levels of TC and HDL-c in HFD. After 6 weeks of Ta, the expression of LXRs in HFD was the same as that in ND in both tissues. The Ta chemical profile was studied with an ultrahigh resolution liquid chromatography Orbitrap MS analysis (UHPLC-PDA-OT-MS/MS). Fifty-one compounds were identified, of which twelve are reported for the first time. Among these compounds, caffeoylquinic acid and its derivatives could modify the lipid profile and the expression of LXRs. This is the first in vivo report of T. absinthioides , which may be a potential candidate against hypercholesterolemia.

This research was designed to investigate the metabolite profiling, phenolics and flavonoids content and the potential antioxidant, antibacterial and nematicidal activities of "yellow-brown resins" from Larrea divaricata Cav (LdRe) and L. nitida Cav (LnRe). Metabolite profiling was obtained using an ultrahigh resolution liquid chromatography orbitrap MS analysis (UHPLC-ESI-OT-MS). The antioxidant properties were screened by four methods: 2,2-diphenyl-1-picrylhydrazyl assay (DPPH), trolox equivalent antioxidant activity assay (TEAC), ferric-reducing antioxidant power assay (FRAP) and lipid peroxidation in erythrocytes (LP). The antibacterial activity was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. In addition, the potential combinatory effect was analyzed with the fractional inhibitory concentration index (FICI) values using the checkerboard design. The nematicidal activity was carried out according to a standardized protocol. LdRe and LnRe showed a strong capture of the DPPH radical withvalues around 8.4 µg resin/mL; FRAP (1.69-1.94 mgTE/ g resin), TEAC (1.08-1.09 mgTE/g resin) and LP (81-82% at 100 µg of resin/mL) assays. A strong antimicrobial activity was displayed by both resins against methicillin-sensitive Staphylococcus aureus ATCC 25923(MSSA) and methicillin-resistant S. aureus ATCC 43300(MRSA) (MICs = 16-32 µg resin/mL). Additionally, the combination of LdRe or LnRe with the antibiotic cefotaxime showed an indifferent effect (FICI values = 1-1.25), however, this combinationcould be a potential strategy to reduce the drug doses, and in this way can be a potential alternative to reduce bacterial resistance. On the other hand, the resins showed a scarce nematicidal potential toward J2 Meloidogyne incognita ; an important nematode infecting horticultural crops. Phenolics compounds were identified by UHPLC-PDA-OT-MS analysis, updating the knowledge on the chemical profile of these species. These results, together with the high content of quantified phenolics and flavonoids, allow the phenolics-enriched resins of these two Larrea species to be considered as a promising sustainable source of compounds of pharmacological interest.

Plants in the Amaryllidaceae family synthesize a diversity of bioactive alkaloids. Some of these plant species are not abundant and have a low natural multiplication rate. The aims of this work were the alkaloids analysis of a Habranthus cardenasianus bulbs extract, the evaluation of its inhibitory activity against cholinesterases, and to test several propagation strategies for biomass production. Eleven compounds were characterized by GC-MS in the alkaloid extract, which showed a relatively high proportion of tazettine. The known alkaloids tazettine, haemanthamine, and the epimer mixture haemanthidine/6-epi-haemanthidine were isolated and identified by spectroscopic methods. Inhibitory cholinesterases activity was not detected. Three forms of propagation were performed: bulb propagation from seed, cut-induced bulb division, and micropropagated bulbs. Finally, different imbibition and post-collection times were evaluated in seed germination assays. The best propagation method was cut-induced bulb division with longitudinal cuts into quarters (T1) while the best conditions for seed germination were 0-day of post-collection and two days of imbibition. The alkaloids analyses of the H. cardenasianus bulbs showed that they are a source of anti-tumoral alkaloids, especially pretazettine (tazettine) and T1 is a sustainable strategy for its propagation and domestication to produce bioactive alkaloids.

Pathogenic bacteria have the ability to develop antibiotic resistance mechanisms. Their action consists mainly in the production of bacterial enzymes that inactivate antibiotics or the appearance of modifications that prevent the arrival of the drug at the target point or the alteration of the target point itself, becoming a growing problem for health systems. Chitosan-gold nanoparticles (Cs-AuNPs) have been shown as effective bactericidal materials avoiding damage to human cells. In this work, Cs-AuNPs were synthesized using chitosan as the reducing agent, and a systematic analysis of the influence of the synthesis parameters on the size and zeta potential of the Cs-AuNPs and their UV-vis spectra was carried out. We used a simulation model to characterize the interaction of chitosan with bacterial membranes, using a symmetric charged bilayer and two different chitosan models with different degrees of the chitosan amine protonation as a function of pH, with the aim to elucidate the antibacterial mechanism involving the cell wall disruption. The Cs-AuNP antibacterial activity was evaluated to check the simulation model.

This research was designed to investigate the metabolite profiling, phenolics, and flavonoids content as well as the potential antioxidant and antibacterial, properties of orange-yellow resin from Zuccagnia punctata Cav (ZpRe). Metabolite profiling was obtained by a ultrahigh resolution liquid chromatography orbitrap MS analysis (UHPLC-ESI-OT-MS-MS). The antioxidant properties were screened by four methods: 2,2-diphenyl-1-picrylhydrazyl assay (DPPH), trolox equivalent antioxidant activity assay (TEAC), ferric-reducing antioxidant power assay (FRAP), and lipid peroxidation in erythrocytes (LP)). The antibacterial activity was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) rules. The resin displayed a strong DPPH scavenging activity (IC 50 = 25.72 µg/mL) and showed a percentage of inhibition of LP close to that of the reference compound catechin (70% at 100 µg ZpRe/mL), while a moderated effect was observed in the FRAP and TEAC assays. The resin showed a content of phenolic and flavonoid compounds of 391 mg GAE/g and 313 mg EQ/g respectively. Fifty phenolics compounds were identified by ultrahigh resolution liquid chromatography orbitrap MS analysis (UHPLC-PDA-OT-MS) analysis. Thirty-one compounds are reported for the first time, updating the knowledge on the chemical profile of this species. The importance of the biomolecules identified support traditional use of this endemic plant. Furthermore, additional pharmacological data is presented that increase the potential interest of this plant for industrial sustainable applications.

The decoction of Tessaria absinthioides is used in traditional medicine of South America as hypocholesterolemic, balsamic, and expectorant; but it is also useful for the prevention of hepatitis, renal insufficiency, and diabetes, and is used as digestive. A lyophilized decoction from the aerial parts of this plant (TLD) collected in San Juan (TLDSJ) and Mendoza (TLDM) provinces (Argentina) and one collection from Antofagasta, Chile (TLDCH) were characterized regarding antioxidant and antibacterial activities, phenolics and flavonoids content, and ultrahigh resolution liquid chromatography Orbitrap MS analysis UHPLC-PDA-OT-MS/MS metabolite profiling. The antioxidant properties were carried out "in vitro" using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and trolox equivalent antioxidant activity (TEAC) methods, ferric-reducing antioxidant power (FRAP), and lipoperoxidation in erythrocytes (LP). The antibacterial activity was evaluated following the Clinical and Laboratory Standards Institute (CLSI) rules. TLDSJ, TLDM, and TLDCH displayed a strong DPPH scavenging activity (EC 50 = 42, 41.6, and 43 µg/mL, respectively) and inhibition of lipoperoxidation in erythrocytes (86-88% at 250 µg TLD/mL), while a less effect in the FRAP and TEACantioxidant assays was found. Additionally, the decoctions showed a content of phenolics compounds of 94 mg gallic acid equivalents (GAE)/g, 185 GAE/g, and 64 GAE/g, for TLDSJ, TLDM, and TLDCH samples, respectively. Regarding the flavonoid content, the Chilean sample was highlighted with 19 mg quercetin equivalents (QE)/g. In this work, several phenolic compounds, including sesquiterpenes, flavonoids, and phenolic acids, were rapidly identified in TLDSJ, TLDM, and TLDCH extracts by means UHPLC-PDA-OT-MS/MS for the first time, which gave a first scientific support to consider this medicinal decoction from both countries as a valuable source of metabolites with antioxidant effects, some with outstanding potential to improve human health.

The decoction of the local plant Baccharis grisebachii is used as a digestive, gastroprotective, external cicatrizing agent and antiseptic in Argentine. A lyophilized decoction (BLD) from the aerial parts of this plant was evaluated regarding its anti-ulcer, antioxidant and cytotoxic activities and the bioactivities were supported by UHPLC-MS metabolome fingerprinting which revealed the presence of several small bioactive compounds. The antioxidant properties were evaluated by DPPH, TEAC, FRAP and lipoperoxidation inhibition in erythrocytes methods, and the antibacterial activity was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The BLD showed a moderate free radical scavenging activity in the DPPH (EC 50 = 106 µg/mL) and lipid peroxidation in erythrocytes assays (67%, at 250 µg/mL). However, the BLD had the highest gastroprotective effect at a dose of 750 mg/kg with a ninety-three percent inhibition of damage through a mechanism that involve NO and prostaglandins using the ethanol-induced gastric damage in a standard rat model. On the other hand, BLD does not induce cytotoxic changes on human tumor and no-tumor cell lines at the concentrations assayed. Regarding the metabolomic analysis, thirty-one compounds were detected and 30 identified based on UHPLC-OT-MS including twelve flavonoids, eleven cinnamic acid derivatives, one coumarin, one stilbene and two other different phenolic compounds. The results support that the medicinal decoction of Baccharis grisebachii is a valuable natural product with gastroprotective effects and with potential to improve human health that opens a pathway for the development of important phytomedicine products.

Background: Embelin (EMB), obtained from Oxalis erythrorhiza Gillies ex Hooker et Arnott (Oxalidaceae), was reported against Trypanosoma cruzi and Leishmania spp. Additionally, antiprotozoan activity against Plasmodium falciparum was reported for its methylated derivative (ME)., Purpose: To evaluate the potential anti-Trypanosoma cruzi activity of EMB, ME and 2,5-di-O-methylembelin (DME) and analyze the possible mechanism of action., Study Design/methods: EMB was isolated by a chromatographic method from the air-dried ground whole plant. To evaluate the effects of methylation, ME and DME were synthesized and tested against T. cruzi epimastigotes and trypomastigotes. The most active compound ME was evaluated against amastigotes. Ultrastructural alterations, ROS generation and the effect on mitochondrial activity of ME were measured., Results: Compounds inhibited the proliferation of epimastigotes. ME was also active against intracellular amastigotes. Mitochondrial alterations were observed by TEM. Additionally, ME modified the mitochondrial activity, and induced an increase in ROS levels. These evidences postulate the mitochondrion as a possible target of ME., Conclusion: ME inhibited amastigotes proliferation, thus being a potential lead compound for the treatment of Chagas' disease., (Copyright © 2018. Published by Elsevier GmbH.)

The seriated extracts of petroleum ether (PE-E), dichloromethane (DCM-E) and methanol extracts (MeOH-E) from the aerial parts of the native South American plant Tetraglochin ameghinoi (Rosaceae), were evaluated regarding their antioxidant and antibacterial activities. The antioxidant properties were evaluated by free radical scavenging methods (DPPH and TEAC), ferric-reducing antioxidant power (FRAP) and lipoperoxidation in erythrocytes (LP), while the antibacterial activity was performed against Gram-positive and Gram-negative bacteria according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The chemical and biological analyses of this plant are very important since this bush is currently used in traditional medicine as a cholagogue and digestive. The polar MeOH-E showed the highest antioxidant activities (17.70 µg/mL in the DPPH assay, 381.43 ± 22.38 mM TE/g extract in the FRAP assay, 387.76 ± 91.93 mg TE/g extract in the TEAC assay and 93.23 + 6.77% in the LP assay) and it was selected for chromatographic isolation of its components. These components were found to be four acetophenones, including the new phloracetophenone glucoside: 4',6',-dihydroxy-2'- O -(6″-acetyl)- β -d-glucopyranosylacetophenone or IUPAC name: (6-(2-acetyl-3,5-dihydroxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)methyl acetate, whose structure was elucidated by NMR and MS methods. In addition, twenty-six compounds, including five of these acetophenone derivatives, two sugars, six flavonoids, eleven phenolic acids and two triterpenes, were identified based on UHPLC-OT-MS and PDA analysis on the MeOH-E. The results support the medicinal use of the plant., Competing Interests: The authors declare no conflict of interest.

Background: In Argentina, the Amaryllidaceae family (59 species) comprises a wide variety of genera, only a few species have been investigated as a potential source of cholinesterases inhibitors to treat Alzheimer disease (AD)., Purpose: To study the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of the basic dichloromethane extracts (E) from Hieronymiella aurea, H. caletensis, H. clidanthoides, H. marginata, and H. speciosa species, as well as the isolated compounds from these plant extracts., Study Design and Methods: AChE and BChE inhibitory activities were evaluated with the Ellman's spectrophotometric method. The alkaloids composition from the E was obtained by gas chromatography-mass spectrometry (GC-MS). The E were successively chromatographed on a silica gel column and permeated on Sephadex LH-20 column to afford the main alkaloids identified by means of spectroscopic data. Additionally, an in silico study was carried out., Results: Nine known alkaloids were isolated from the E of five Hieronymiella species. Galanthamine was identified in all the species by GC-MS standing out H. caletensis with a relative abundance of 9.79% of the total ion current. Strong AChE (IC 50  = 1.84 - 15.40 µg/ml) and moderate BChE (IC50 = 23.74 - 136.40 µg/ml) inhibitory activities were displayed by the extracts. Among the isolated alkaloids, only sanguinine and chlidanthine (galanthamine-type alkaloids) demonstrated inhibitory activity toward both enzymes. The QTAIM study suggests that sanguinine has the strongest affinity towards AChE, attributed to an additional interaction with Ser200 as well as stronger molecular interactions Glu199 and His440.These results allowed us to differentiate the molecular behavior in the active site among alkaloids possessing different in vitro inhibitory activities., Conclusion: Hieronymiella species growing in Argentina represent a rich and widespread source of galanthamine and others AChE and BChE inhibitors alkaloids. Additionally, the new trend towards the use of natural extracts as pharmaceuticals rather than pure drugs opens a pathway for the development of a phytomedicine derived from extracts of Hieronymiella spp., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

The emergence of old and new antibiotic resistance created in the last decades revealed a substantial medical need for new classes of antimicrobial agents. The antimicrobial activity of sulfa drugs is often enhanced by complexation with metal ions, which is in concordance with the well-known importance of metal ions in biological systems. Besides, sulfonamides and its derivatives constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anti-carbonic anhydrase, diuretic, hypoglycemic, antithyroid, antiviral and anticancer activities, among others. The purpose of this work has been the obtainment, characterization and determination of biological properties (antibacterial, antifungal, mutagenicity and phytotoxicity) of a new Co(III)-sulfathiazole complex: Costz, besides of its interaction with bovine serum albumin (BSA). The reaction between sodium sulfathiazole (Nastz) and cobalt(II) chloride in the presence of H 2 O 2 leads to a brown solid, [Co III (stz) 2 OH(H 2 O) 3 ], (Costz). The structure of this compound has been examined by means of elemental analyses, FT-IR, 1 H NMR, UV-Visible spectrometric methods and thermal studies. The Co(III) ion, which exhibits a distorted octahedral environment, could coordinate with the N thiazolic atom of sulfathiazolate. The complex quenched partially the native fluorescence of bovine serum albumin (BSA), suggesting a specific interaction with the protein. The Costz complex showed, in vitro, a moderate antifungal activity against Aspergillus fumigatus and A. flavus. As antibacterial, Costz displayed, in vitro, enhanced activity respective to the ligand against Pseudomonas aeruginosa. Costz did not show mutagenic properties with the Ames test. In the Allium cepa test the complex showed cytotoxic properties but not genotoxic ones. These results may be auspicious, however, further biological studies are needed to consider the complex Costz as a possible drug in the future., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Two new alkaloids, 4-O-methylnangustine (1) and 7-hydroxyclivonine (2) (montanine and homolycorine types, respectively), and four known alkaloids were isolated from the bulbs of Hippeastrum argentinum, and their cholinesterase-inhibitory activities were evaluated. These compounds were identified using GC-MS, and their structures were defined by physical data analysis. Compound 2 showed weak butyrylcholinesterase (BuChE)-inhibitory activity, with a half-maximal inhibitory concentration (IC50) value of 67.3 ± 0.09 μM. To better understand the experimental results, a molecular modeling study was also performed. The combination of a docking study, molecular dynamics simulations, and quantum theory of atoms in molecules calculations provides new insight into the molecular interactions of compound 2 with BuChE, which were compared to those of galantamine.

In order to searching a potential novel approach to pistachio utilization, the chemical and nutritional quality of oil and flour from natural, roasted, and salted roasted pistachios from Argentinian cultivars were evaluated. The pistachio oil has high contents of oleic and linoleic acid (53.5 - 55.3, 29 - 31.4 relative abundance, respectively), tocopherols (896 - 916 μg/g oil), carotenoids (48 - 56 μg/g oil) and chlorophylls (41 - 70 μg/g oil), being a good source for commercial edible oil production. The processing conditions did not affect significantly the fatty acid and minor composition of pistachio oil samples. The content of total phenolic (TP) and flavonoids (FL) was not significantly modified by the roasting process, whereas free radical scavenging (DPPH radical) and antioxidant power decreased in a 20% approximately. Furthermore, salted roasted pistachio flour (SRPF) showed a significant decrease in TP and FL content in comparison to others samples. The phenolic profile of pistachio flours evaluated by LC-ESI-QTOF-MS. The major compounds identified were (+)-catechin (38 - 65.6 μg/g PF d.w.), gallic acid (23 - 36 μg/g PF d.w.) and cyanidin-3-O-galactoside (21 - 23 μg/g PF d.w.). The treatments effects on the phenolics constituents of pistachio flour. Roasting caused a significant reduction of some phenolics, gallic acid and (+)- catechin, and increased others, naringenin and luteolin. Salting and roasting of pistachio increased garlic acid and naringenin content.

A series of dihydropyran embelin derivatives was synthesized through a direct and highly efficient approach based on a domino Knoevenagel intramolecular hetero-Diels-Alder reaction from natural embelin (1), using unsaturated aldehydes in the presence of organocatalysts such as ethylendiamine diacetate or l-proline. The aliphatic aldehydes yielded exclusively trans adducts, while mixtures of trans and cis isomers were found in reactions with aromatic aldehydes, with the cis form always predominating. Some of the compounds obtained were active and selective against Gram-positive bacteria, including multiresistant Staphylococcus aureus clinical isolates.

Unlabelled: The antimicrobial activity of Bolivian propolis was assessed for the first time on a panel of bacteria and two endemic parasitic protozoa. Ten samples of Bolivian propolis and their main constituents were tested using the micro-broth dilution method against 11 bacterial pathogenic strains as well as against promastigotes of Leishmania amazonensis and L. braziliensis using the XTT-based colorimetric method. The methanolic extracts showed antibacterial effect ranging from inactive (MICs > 1000 μg ml(-1) ) to low (MICs 250-1000 μg ml(-1) ), moderate (62·5-125 μg ml(-1) ) and high antibacterial activity (MIC 31·2 μg ml(-1) ), according to the collection place and chemical composition. The most active samples towards Leishmania species were from Cochabamba and Tarija, with IC50 values of 12·1 and 7·8, 8·0 and 10·9 μg ml(-1) against L. amazonensis and Leishmania brasiliensis respectively. The results show that the best antibacterial and antiprotozoal effect was observed for some phenolic-rich propolis., Significance and Impact of the Study: Propolis is used in Bolivia as an antimicrobial agent. Bolivian propolis from the main production areas was assessed for antibacterial and leishmanicidal effect and the results were compared with the propolis chemical composition. The active antibacterial propolis samples were phenolic-rich while those containing mainly triterpenes were devoid of activity or weakly active. A similar picture was obtained for the effect on Leishmania, with better effect for the phenolic-rich samples. As propolis is used for the same purposes regardless of the production area and composition, our findings indicate the need for the standardization of this natural product as antimicrobial., (© 2016 The Society for Applied Microbiology.)

Objectives: Many natural antioxidants have poor pharmacokinetic properties that impair their therapeutic use. For hydroxycinnamic acids (HCAs) and other phenolic antioxidants, their major drawback is their low lipophilicity and a rapid metabolism. The difluoromethyl group may be considered as a 'lipophilic hydroxyl' due to its hydrogen bond donor and acceptor properties; this prompted us to assess it as a bioisosteric replacement of a phenolic hydroxyl for increasing the lipophilicity of HCAs., Methods: Six difluoromethyl-substituted methyl cinnamates (4a-c, 5a-c) related to caffeic acid were synthesized and their antioxidant activity evaluated by chemical (FRAP, DPPH scavenging, inhibition of β-carotene bleaching, at 1-200 μm), electrochemical (differential pulse voltammetry, cyclic voltammetry) and cell-based (inhibition of lipid peroxidation in erythrocytes, at 1 and 50 μm) assays., Key Fndings: Analogues 4a-c and 5a-c were inactive in FRAP and DPPH assays and only those containing a free phenolic hydroxyl (4a and 5a) exhibited electrochemical activity although with high redox potentials. Compounds 4a,b and 5a,b were active in the inhibition of β-carotene bleaching assay and all analogues inhibited lipid peroxidation in the human erythrocytes assay., Conclusions: Lipophilic difluoromethyl-substituted cinnamic esters retain radical scavenging capabilities that prove useful to confer antioxidant properties in a non-polar environment., (© 2016 Royal Pharmaceutical Society.)

Background: Zuccagnia punctata Cav. (Fabaceae) and Larrea nitida Cav. (Zygophyllaceae) are indistinctly or jointly used in traditional medicine for the treatment of fungal-related infections. Although their dichloromethane (DCM) extract have demonstrated moderate antifungal activities when tested on their own, antifungal properties of combinations of both plants have not been assessed previously., Purpose: The aim of this study was to establish with statistical rigor whether Z. punctata (ZpE) and L. nitida DCM extract (LnE) interact synergistically against the clinically important fungi Candida albicans and Candida glabrata and to characterize the most synergistic combinations., Study Design: For synergism assessment, the statistical-based Boik's design was applied. Eight ZpE-LnE fixed-ratio mixtures were prepared from four different months of 1 year and tested against Candida strains. Lϕ (Loewe index) of each mixture at different fractions affected (ϕ) allowed for the finding of the most synergistic combinations, which were characterized by HPLC fingerprint and by the quantitation of the selected marker compounds., Methods: Lϕ and confidence intervals were determined in vitro with the MixLow method, once the estimated parameters from the dose-response curves of independent extracts and mixtures, were obtained. Markers (four flavonoids for ZpE and three lignans for LnE) were quantified in each extract and their combinations, with a valid HPLC-UV method. The 3D-HPLC profiles of the most synergistic mixtures were obtained by HPLC-DAD., Results: Three over four IC50ZpE/IC50LnE fixed-ratio mixtures displayed synergistic interactions at effect levels ϕ > 0.5 against C. albicans. The dosis of the most synergistic (Lϕ = 0.62) mixture was 65.96 µg/ml (ZpE = 28%; LnE = 72%) containing 8 and 36% of flavonoids and lignans respectively. On the other hand, one over four IC50ZpE/IC50LnE mixtures displays synergistic interactions at ϕ > 0.5 against C. glabrata. The dosis of the most synergistic (Lϕ = 0.67) mixture was 168.23 µg/ml (ZpE = 27%; LnE = 73%) with 9.7 and 31.6% of flavonoids and lignans respectively., Conclusions: Studies with the statistical-based MixLow method, allowed for the finding of the most ZpE-LnE synergistic mixtures, giving support to a proper joint use of both antifungal herbs in traditional medicine., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

New nitrosopyrimidines were synthesized and evaluated as potential antibacterial agents. Different compounds structurally related with 4,6-bis(alkyl or arylamino)-5-nitrosopyrimidines were evaluated. Some of these nitrosopyrimidines displayed significant antibacterial activity against human pathogenic bacteria. Among them compounds 1c, 2a-c, and 9a-c exhibited remarkable activity against methicillin-sensitive and -resistant Staphylococcus aureus, Escherichia coli, Yersinia enterocolitica, and Salmonella enteritidis. A detailed structure-activity relationship study, supported by theoretical calculations, aided us to identify and understand the minimal structural requirements for the antibacterial action of the nitrosopyrimidines reported here. Thus, our results have led us to identify a topographical template that provides a guide for the design of new nitrosopyrimidines with antibacterial effects., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Ethnopharmacological Relevance: Animal oils and fats from the fishes Electrophorus electricus and Potamotrygon motoro, the reptiles Boa constrictor, Chelonoidis denticulata (Geochelone denticulata) and Melanosuchus niger and the riverine dolphin Inia geoffrensis are used as anti-inflammatory agents in the Peruvian Amazon. The aim of the study was to assess the topic anti-inflammatory effect of the oils/fats as well as to evaluate its antimicrobial activity and fatty acid composition., Materials and Methods: The oils/fats were purchased from a traditional store at the Iquitos market of Belen, Peru. The topic anti-inflammatory effect was evaluated by the mice ear edema induced by arachidonic acid (AA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) at the dose of 3mg oil/ear. Indomethacine and nimesulide were used as reference anti-inflammatory drugs. The application resembles the traditional topical use of the oils. The antimicrobial effect of the oils/fats was assessed by the microdilution test against reference strains of Escherichia coli, Staphylococcus aureus and Salmonella enteritidis. The fatty acid composition of the oils/fats (as methyl esters) was determined by GC and GC-MS analysis after saponification., Results: All oils/fats showed topic anti-inflammatory activity, with better effect in the TPA-induced mice ear edema assay. The most active drugs were Potamotrygon motoro, Melanosuchus niger and Geochelone denticulata. In the AA-induced assay, the best activity was found for Potamotrygon motoro and Electrophorus electricus oil. The oil of Electrophorus electricus also showed a weak antimicrobial effect with MIC values of 250 µg/mL against Escherichia coli ATCC 25922 and Salmonella enteritidis-MI. The main fatty acids in the oils were oleic, palmitic and linoleic acids., Conclusions: Topical application of all the oils/fats investigated showed anti-inflammatory activity in the mice ear edema assay. The effect can be related with the identity and composition of the fatty acids in the samples. This study gives support to the traditional use of animal oils/fats as ant-inflammatory agents in the Peruvian Amazon. However, new alternative should be encouraged due to the conservation status of several of the animal sources of the crude drugs., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The Amaryllidaceae family is well known for its pharmacologically active alkaloids. An important approach to treat Alzheimer’s disease involves the inhibition of the enzyme acetylcholinesterase (AChE). Galanthamine, an Amaryllidaceae alkaloid, is an effective, selective, reversible, and competitive AchE inhibitor. This work was aimed at studying the alkaloid composition of four wild Argentinian Amarillydaceae species for the first time, as well as analyzing their inhibitory activity on acetylcholinesterase. Alkaloid content was characterized by means of GC-MS analysis. Chloroform basic extracts from Habranthus jamesonii, Phycella herbertiana, Rhodophiala mendocina and Zephyranthes filifolia collected in the Argentinian Andean region all contained galanthamine, and showed a strong AChE inhibitory activity (IC50 between 1.2 and 2 µg/mL). To our knowledge, no previous reports on alkaloid profiles and AChEIs activity of wild Argentinian Amarillydaceae species have been publisihed. The demand for renewable sources of industrial products like galanthamine and the need to protect plant biodiversity creates an opportunity for Argentinian farmers to produce such crops.

The essential oils (EOs) of two populations of Azorella cryptantha (Clos) Reiche, a native species from San Juan Province, were obtained by hydrodistillation in a Clevenger-type apparatus and characterized by GC-FID and GC/MS analyses. The compounds identified amounted to 92.3 and 88.7% of the total oil composition for A. cryptantha from Bauchaceta (Ac-BAU) and Agua Negra (Ac-AN), respectively. The EO composition for the two populations was similar, although with differences in the identity and content of the main compounds and also in the identity of minor components. The main compounds of the Ac-BAU EO were α-pinene, α-thujene, sabinene, δ-cadinene, δ-cadinol, trans-β-guaiene, and τ-muurolol, while α-pinene, α-thujene, β-pinene, γ-cadinene, τ-cadinol, δ-cadinene, τ-muurolol, and a not identified compound were the main constituents of the Ac-AN EO, which also contained 3.0% of oxygenated monoterpenes. The repellent activity on Triatoma infestans nymphs was 100 and 92% for the Ac-AN and Ac-BAU EOs, respectively. Regarding the toxic effects on Ceratitis capitata, the EOs were very active with LD(50) values lower than 11 μg/fly. The dermatophytes Microsporum gypseum, Trichophyton rubrum, and T. mentagrophytes and the bacterial strains Escherichia coli LM(1), E. coli LM(2), and Yersinia enterocolitica PI were more sensitive toward the Ac-AN EO (MIC 125 μg/ml) than toward the Ac-BAU EO. This is the first report on the composition of A. cryptantha EO and its anti-insect and antimicrobial properties., (Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.)

The infusion of the aerial parts of Gentianella multicaulis (Gillies ex Griseb.) Fabris (Gentianaceae), locally known as 'nencia', is used in San Juan Province, Argentina, as stomachic and as a bitter tonic against digestive and liver problems. The bioassay-guided isolation of G. multicaulis extracts and structural elucidation of the main compounds responsible for the antifungal and free radical scavenging activities were performed. The extracts had strong free radical scavenging effects in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay (45-93% at 10 microg/mL) and ferric-reducing antioxidant power (FRAP) assay at 200 microg/mL. Demethylbellidifolin (4) had high antioxidant activity in the DPPH and FRAP assay. The dermatophytes Microsporum gypseum, Trichophyton mentagrophytes, and T. rubrum were moderately inhibited by the different extracts (MIC values of 125-250 microg/mL). Demethylbellidifolin (4), bellidifolin (5), and isobellidifolin (6) showed an antifungal effect (MIC values of 50 microg/mL), while swerchirin (3) was less active with a MIC value of 100 microg/mL. In addition, oleanolic acid (1) and ursolic acid (2) were also isolated. These findings demonstrate that Gentianella multicaulis collected in the mountains of the Province of San Juan, Argentina, is an important source of compounds with antifungal and antioxidant activities.

The chemical profile and botanical origin of Andean Argentinian propolis were studied by HPLC-ESI-MS/MS and GC-MS techniques as well as the antifungal activity according to CLSI protocols. Dermatophytes and yeasts tested were strongly inhibited by propolis extracts (MICs between 31.25 and 125 μg/mL). The main antifungal compounds were: 3'methyl-nordihydroguaiaretic acid (MNDGA) 1, nordihydroguaiaretic acid (NDGA) 2 and a NDGA derivative 3, showing strong activity against Trichophyton mentagrophytes, T. rubrum and Microsporum gypseum (MICs between 15.6 and 31.25 μg/mL). The lignans 1 and 2 showed activities against clinical isolates of Candidas spp., Cryptococcus spp., T. rubrum and T. mentagrophytes (MICs and MFCs between 31.25 and 62.5 μg/mL). The lignan and volatile organic compounds (VOCs) profiles from propolis matched with those of exudates of Larrea nitida providing strong evidences on its botanical origin. These results support that Argentinian Andean propolis are a valuable natural product with potential to improve human health. Six compounds (1-6) were isolated from propolis for the first time, while compounds 1 and 3-6 were reported for first time as constituents of L. nitida Cav., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Essential oils from four species of the genus Tagetes L. (Asteraceae, Helenieae) collected in Tucumán province, Argentina, were evaluated for their chemical composition, toxicity, and olfactory activity on Mediterranean fruit fly Ceratitis capitata Wiedemann adults and for repellent properties on Triatoma infestans (Klug) (Chagas disease vector). Yields of essential oils range from 0.2 to 0.8% (v/w). The same main constituents among Tagetes minuta L., Tagestes rupestris Cabrera, and Tagetes terniflora Kunth, (cis-trans)-ocimenes, (cis-trans)-tagetones, and (cis-trans)-ocimenones showed important differences in their relative compositions. Tagetes filifolia Lag. was characterized by the recognized phenylpropanoids methylchavicol and trans-anethole as the main components. LD(50) was ≤20 μg/insect in topical bioassays. T. rupestris was the most toxic to C. capitata females, whereas the other oils presented similar toxicities against males and females. Tagetes rupestris oil attracted both sexes of C. capitata at 5 μg, whereas T. minuta showed opposite activities between males (attractant) and females (repellent). Oils from T. minuta and T. filifolia were the most repellent to T. infestans. The results suggest that compositions of essential oils influence their insecticidal and olfactory properties. The essential oils from Tagetes species show an important potential as infochemical agents on insects' behaviors. This study highlights the chemical variability of essential oils as a source of variation of anti-insect properties.

The antifungal, antibacterial, and insect-repellent activities of the essential oils (EOs) of Acantholippia seriphioides, Artemisia mendozana, Gymnophyton polycephalum, Satureja parvifolia, Tagetes mendocina, and Lippia integrifolia, collected in the Central Andes area, province of San Juan, Argentina, were investigated. The dermatophytes Microsporum gypseum, Trichophyton mentagrophytes, and T. rubrum were inhibited by the EOs of G. polycephalum, L. integrifolia, and S. parvifolia, with minimum inhibitory concentrations (MICs) between 31.2 and 1000 μg/ml. Moreover, all EOs presented moderate activity against the bacteria tested, and the L. integrifolia and G. polycephalum EOs showed excellent repellent properties against Triatoma infestans, the Chagas disease vector, with repellency values between 60 and 100%. The A. seriphioides, G. polycephalum, and L. integrifolia EOs, obtained by hydrodistillation, were characterized by GC-FID and GC/MS analyses. The highest number of components (40) was identified in L. integrifolia EO, which, along with that of A. seriphioides, contained important amounts of oxygenated monoterpenes (44.35 and 29.72%, resp.). Thymol (27.61%) and carvacrol (13.24%) were the main components of A. seriphioides EO, and borneol, lippifoli-1(6)-en-5-one, and terpinen-4-ol (>8.5%) were the principal compounds of L. integrifolia EO. These results support the idea that oxygenated monoterpenes are the bioactive fractions of the EOs. Finally, the study shows that these Andean species might be used to treat superficial fungal infections and to improve the local Chagas disease situation by vector-control., (Copyright © 2011 Verlag Helvetica Chimica Acta AG, Zürich.)

The petroleum ether extract of Baccharis darwinii showed activity against Cryptococcus neoformans and dermatophytes. Bioactivity-guided fractionation of Baccharis darwinii has resulted in the isolation of three coumarins: 5'-hydroxy aurapten (anisocoumarin H, 1), aurapten (7-geranyloxycoumarin, 2) and 5'-oxoaurapten (diversinin, 3). The structures of these compounds were characterized by spectroscopic methods. These compounds were evaluated for their antimicrobialactivity against a panel of each, bacteria and fungi. Compound 3 showed the best activities against Microsporum gypseum, Trichophyton rubrum and Trichophyton mentagrophytes with MICs = 15.6 microg/mL, followed by compound 1 whose MICs against the same fungi were 62.5 microg/mL. In addition they showed fungicidal rather than fungistatic activity. Both compounds showed moderate activity (MICs = 125 microg/mL) against Cryptococcus neoformans. This is the first report of the presence of compound 1 in B. darwinii.

This paper reports the in vitro antifungal activity of propolis extracts from the province of Tucuman (Argentina) as well as the identification of their main antifungal compounds and botanical origin. The antifungal activity was determined by the microdilution technique, using reference microorganisms and clinical isolates. All dermatophytes and yeasts tested were strongly inhibited by different propolis extracts (MICs between 16 and 125 microg mL(-1)). The most susceptible species were Microsporum gypseum, Trichophyton mentagrophytes, and Trichophyton rubrum. The main bioactive compounds were 2',4'-dihydroxy-3'-methoxychalcone 2 and 2',4'-dihydroxychalcone 3. Both displayed strong activity against clinical isolates of T. rubrum and T. mentagrophytes (MICs and MFCs between 1.9 and 2.9 microg mL(-1)). Additionally, galangin 5, pinocembrin 6, and 7-hydroxy-8-methoxyflavanone 9 were isolated from propolis samples and Zuccagnia punctata exudates, showing moderate antifungal activity. This is the first study matching the chemical profile of Z. punctata Cav. exudates with their corresponding propolis, giving strong evidence on the botanical origin of the studied propolis.

The chemical characterization as well as the assessment of geographical origin of propolis from several areas of the Provincia de San Juan (Argentina) is reported. Chemical characterization of propolis was performed by measuring total phenolic (TP), total flavonoids (FL), free radical scavenging capacity (DPPH bleaching), and metal content in samples of six different districts. Methanolic propolis extracts (MEP) showed TP ranging from 25.7 to 39.3 g of gallic acid equivalents per 100 g of MEP, whereas flavonoids ranged from 6.6 to 13.3 g of quercetin equivalents per 100 g of MEP. Six main flavonoids were isolated and identified from the propolis samples, comprising the flavanones 7-hydroxy-8-methoxyflavanone (1), pinocembrin (2), and pinobanksin (3), the flavones chrysin (4) and tectochrysin (5), and the flavonol galangin (6). Compounds 1-6 were quantified by HPLC-PDA. Free radical scavenging activity, measured as percent DPPH bleaching, ranged from 46.6 to 89.5 at 10 mug/mL. Moreover, propolis samples presented high contents of Ca, K, Fe, Na, and Mg, but low amounts of Mn and Zn. Linear discriminant analysis affords eight descriptors, galangin, pinocembrin, pinobanksin, chrysin, tectochrysin, DPPH, K, and Na, allowing a clear distinction with 100% accuracy among different origins within the Provincia de San Juan. A direct relationship of DPPH free radical scavenging activity with TP or with compounds 1-6 was not found, showing the need of further evaluation on the origin of free radical activity in propolis samples.

Extracts from the Andean lichens Protousnea poeppigii and Usnea florida displayed antimicrobial activity against the pathogenic fungi Microsporum gypseum, Trichophyton mentagrophytes and T. rubrum with MIC values between 50 and 100 microg/mL. From the active extracts, four main metabolites were isolated and identified as the new depside, isodivaricatic acid, and the known metabolites 5-propylresorcinol, divaricatinic acid and usnic acid. Isodivaricatic acid and divaricatinic acid presented antifungal effect towards M. gypseum with a MIC of 50 microg/mL and against T. mentagrophytes and T. rubrum and with MIC values of 50 and 100 microg/mL, respectively. The new isodivaricatic acid was active towards Leishmania amazonensis, Leishmania brasiliensis and Leishmania infantum promastigotes with 100% lysis at 100 microg/mL.The activity of the new compound decreased on acetylation of the hydroxy groups as well as on methylation of the acid function. The structures were elucidated by spectroscopic means. The spectroscopic data of isodivaricatic acid are presented here for the first time.

Twelve new withanolides were isolated from the aerial part of Jaborosa rotacea: five had a spiranoid delta-lactone (1-5); one contained a 26,12-delta-lactone and a C-12-C-23 bond (6); five corresponded to trechonolide-type withanolides with configuration at C-23 opposite of those previously isolated (7, 8, 10-12); two of these have an additional oxido-bridge between C-21 and C-24; finally a withanolide with a hemiketal ring formed between a 21-hydroxyl and a 12-ketone (13) and the closely related jaborosalactone R were also isolated. New compounds were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS). The structures of the spiranoid withanolide and of the epimer of trechonolide A were confirmed by X-ray diffraction studies. Compounds 4, 5, 6, and 8 showed selective phytotoxicity toward monocotyledoneous and dicotyledoneous species.

The exudate and seriated extracts from the aerial parts of Baccharis grisebachii (Asteraceae) which is recommended as a digestive and to relieve gastric ulcers in Argentina, showed activity as free radical scavengers and inhibited lipoperoxidation in erythrocytes. Assay-guided isolation led to seven p-coumaric acid derivatives and six flavonoids as the main active constituents of the crude drug. The activity towards the superoxide anion was mainly due to the flavonoid constituents. 5,7,4'-Trihydroxy-6-methoxyflavone and quercetin presented high activity (64 and 79%) even at 12.5 microg/ml. The xanthine oxidase inhibitory effect of the extracts can be related with the p-coumaric acid derivatives drupanin, 4-acetyl-3,5-diprenylcinnamic acid and trans-ferulic acid O-hexan-3-onyl-ether which showed IC(50) values in the range 28-40 microg/ml. Both p-coumaric acid derivatives and flavonoids inhibited lipoperoxidation in erythrocytes. The highest activity was found for the p-coumaric acid derivatives 4-acetyl-3-prenyl-ethoxycinnamate, 3-prenyl-4-(4'-hydroxydihydrocinnamoyloxy)-cinnamate and trans-ferulic acid O-hexan-3-onyl-ether (69-82%) and the flavonoids 5,7,4'-trihydroxy-6-methoxyflavone, quercetin, 5,7,4'-trihydroxy-6,3'-dimethoxyflavone and 5,7,4'-trihydroxy-6,8-dimethoxyflavone (64-84%) at 100 microg/ml. The most active free radical scavengers measured by the DPPH decoloration assay were the p-coumaric acid derivatives drupanin and trans-ferulic acid O-hexan-3-onyl-ether (27-35% at 10 microg/ml) and the flavonoid quercetin (97 and 23% at 10 and 1 microg/ml, respectively). The results support the use of Baccharis grisebachii in Argentinian traditional medicine.

Tagetes mendocina (Asteraceae) is a medicinal plant widely used in the Andean provinces of Argentina. Preliminary assays showed free radical scavenging activity in the methanol extract of the aerial parts, measured by the decoloration of a methanolic solution of the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and scavenging of the superoxide anion. Assay-guided isolation led to 4'-hydroxyacetophenone (1), protocatechuic acid (2), syringic acid (3), patuletin (4), quercetagetin 7-O-beta-D-glucoside (5), patuletin 7-O-beta-D-glucoside (6) and axillarin 7-O-beta-D-glucoside (7) as the free radical scavengers and antioxidant compounds from Tagetes mendocina. On the basis of dry starting material, the total phenolic content of the crude drug was 3.00% with 0.372% of flavonoids. The content of compounds 1-7 in the crude drug was 0.008, 0.015, 0.010, 0.029, 0.238, 0.058 and 0.017%, respectively. Quercetagetin 7-O-beta-D-glucoside proved to be the main free radical scavenger of the extracts measured by the DPPH decoloration test as well as for quenching the superoxide anion and inhibition of lipoperoxidation in erythrocytes. In the lipid peroxidation assay the percentual inhibition was related with the number of methoxy groups in the molecule, ranging from 86% for the quercetagetin glucoside to 67% for the monomethoxylated and 31% for the dimethoxylated derivative. The compounds showed low cytotoxicity towards human lung fibroblasts with IC50 > 1 mM for compounds 1-3 and 0.24 to 0.52 mM for the flavonoids 4-7.

The resinous exudate of Baccharis grisebachii which is used to treat ulcers, burns, and skin sores in Argentina showed activity towards dermatophytes and bacteria. Two diterpenes, eight p-coumaric acid derivatives, and two flavones were isolated from the exudate and the structures elucidated by spectroscopic methods. 3-Prenyl-p-coumaric acid and 3,5-diprenyl-p-coumaric acid were active towards Epidermophyton floccosum and Trichophyton rubrum with MICs of 50 and 100-125 microg/ml, respectively. The diterpene labda-7,13E-dien-2beta,15-diol was active towards Epidermophyton floccosum and Trichophyton rubrum with MICs of 12.5 microg/ml while the MIC against Microsporum canis and Trichophyton mentagrophytes was 25 microg/ml. The diterpene was also active towards Microsporum gypseum with a MIC of 50 microg/ml, and showed inhibition in both Staphylococcus aureus (methicilline resistant and sensible strains) with MICs of 125 microg/ml. The results support the use of Baccharis grisebachii in Argentinian traditional medicine.

The benzoquinone embelin and four alkyl phenols were isolated from an Argentinean collection of Oxalis erythrorhiza. 3-Heptadecyl-5-methoxy-phenol is reported for the first time. The structures were determined by spectroscopic methods. Embelin presented inhibitory effect on methicillin-resistant Staphylococcus aureus, Escherichia coli and the dermatophytic fungi Epidermophyton floccosum, Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes and Trichophyton rubrum with MICs ranging between 50 and 100 microg/ml. Furthermore, embelin was active against Trypanosoma cruzi trypomastigotes with 100% lysis at 100 microg/ml and cytotoxicity below the trypanocidal concentration. The new alkyl phenol 3-heptadecyl-5-methoxy-phenol was active towards Leishmania amazonensis and Leishmania donovani promastigotes with 100% lysis at 100 microg/ml. The cytotoxicity (IC50) of embelin and the new alkyl phenol on human lung fibroblasts were 739 and 366 microM, respectively. The plant is used to treat heart complains, a symptomatology related to Chagas' disease which is endemic in the San Juan Province, Argentine.

The dry leaves of Peumus boldus (Monimiaceae) are used in infusion or decoction as a digestive and to improve hepatic complains. Preliminary assays showed free-radical scavenging activity in hot water extracts of boldo leaves, measured by the decoloration of a methanolic solution of the 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH). Assay-guided isolation led to the active compounds. Catechin proved to be the main free-radical scavenger of the extracts. Lipid peroxidation in erythrocytes was inhibited by boldo extracts and fractions at 500 microg/ml with higher effect for the ethyl acetate soluble and alkaloid fractions. The IC50 for catechin and boldine in the lipid peroxidation test were 75.6 and 12.5 microg/ml, respectively. On the basis of dry starting material the catechin content in the crude drug was 2.25% while the total alkaloid calculated as boldine was 0.06%. The activity of boldine was six times higher than catechin in the lipid peroxidation assay. However, the mean catechin:total alkaloid content ratio was 37:1. The relative concentration of alkaloids and phenolics in boldo leaves and their activity suggest that free-radical scavenging effect is mainly due to catechin and flavonoids and that antioxidant effect is mainly related with the catechin content The high catechin content of boldo leaves and its bioactivity suggest that quality control of Boldo folium has to combine the analysis of catechin as well as their characteristic aporphine alkaloids.

Extracts of the whole plant Acaena magellanica (Rosaceae) were assessed for anti-inflammatory, antipyretic and analgesic activity in animal models. At 600 mg kg(-1), the global ethanolic extract (GEE), dichloromethane (DCM) and defatted methanol (MeOH) fractions showed a mild anti-inflammatory effect in the carrageenan-induced guinea-pig paw oedema. The GEE, DCM and defatted MeOH fractions significantly reduced inflammation by 43.2, 40.5 and 42.1%, respectively. The GEE did not showed any significant antipyretic activity in doses up to 600 mg kg(-1). A 20% w/v infusion administered orally at 16 mL kg(-1) presented analgesic effect in the acetic acid-induced abdominal constriction test in mice. The GEE and MeOH extract of A. magellanica showed free radical scavenging activity in the diphenylpicrylhydrazyl decolouration assay. Assay-guided isolation led to quercetin, Q-3-O-beta-glucoside, Q-3-O-beta-D-galactoside, ellagic acid and catechin as the free radical scavengers. The saponins tormentic acid 28-O-beta-D-galactopyranoside and 28-O-beta-D-glucopyranoside were isolated from the polar extract. The structures were determined by spectroscopic methods.

Eighteen extracts from Acaena magellanica, Baccharis grisebachii, Ephedra breana, Oxalis erythrorhiza, Pachylaena atriplicifolia and Satureja parvifolia were assessed for antimicrobial activity against bacteria and fungi with the agar dilution method. The hexane (H) and dichloromethane (DCM) extracts of B. grisebachii and O. erythrorhiza showed the broadest spectrum of action against fungi, inhibiting all of the tested dermatophytes with MICs ranging from < or =25 to < or =1000 microg/ml. Trichophyton rubrum was the most susceptible species and Cryptococcus neoformans was inhibited only by the DCM extract of B. grisebachii with MIC of 600 microg/ml. Regarding the antibacterial activity, H and DCM extracts of B. grisebachii as well as the DCM of O. erythrorhiza, were active on methicillin-resistant and methicillin-sensitive Staphylococcus aureus with MIC from < or =125 to < or =500 microg/ml. The DCM extract of B. grisebacchii was more active against methicillin-resistant than methicillin-sensitive strains.

The antibacterial activities and preliminary phytochemical screening of 13 plants used as folk medicine in San Juan, Argentina, are reported.

A novel compound, 1 beta-hydroxydehydroabietic acid has been obtained by the microbial transformation of dehydroabietic acid, using cultures of Fusarium oxysporum and F. moniliforme. Its antibacterial activity was also tested.