Oxonitrogenated Derivatives of Eremophilans and Eudesmans: Antiproliferative and Anti- Activity.

Cancer is one of the most important causes of death worldwide. Solid tumors represent the vast majority of cancers (>90%), and the chemotherapeutic agents used for their treatment are still characterized by variable efficacy and toxicity. Sesquiterpenes are a group of natural compounds that have shown a wide range of biological activities, including cytotoxic and antiparasitic activity, among others.

In vivo photoinduced [4 + 2] dimerization of a neo-clerodane diterpene in Baccharis flabellata. ROS and RNS scavenging abilities.

Secondary metabolites play a major role in the adaptation of plants to the environment. Furan neo-clerodane diterpenes are characteristic secondary metabolites in Baccharis flabellata Hook. & Arn.

Gardenin B-induced cell death in human leukemia cells involves multiple caspases but is independent of the generation of reactive oxygen species.

Flavonoids have attracted great interest due to their possible anticancer activities. Here we investigated the antiproliferative activity of the flavonoids isolated from Baccharis scandens against human leukemia cell lines and found that the methoxyflavonoid gardenin B was the most cytotoxic compound against HL-60 and U-937 cells, showing IC50 values between 1.6 and 3.

A new iridoid, verbascoside and derivatives with inhibitory activity against Taq DNA polymerase.

DNA polymerases are enzymes that play a crucial role in DNA metabolism such as replication, repair, transcription, recombination, and chromosome segregation during mitosis. Herein we report the isolation of a new iridoid (6-epi-catalpol, 2) and per-O-acetyl-verbascoside (11) from aerial part of Buddleja cordobensis Grisebach (Buddlejaceae). From compound 2, we have obtained eight compounds by chemical transformation.

Antibacterial activity of Mulinum spinosum extracts against slime-producing Staphylococcus aureus and methicillin-resistant Staphylococcus aureus isolated from nasal carriers.

Nasal carriers of Staphylococcus aureus are important reservoirs with risk of developing endogenous infections or transmitting infections to susceptible individuals. Methicillin-resistant S. aureus (MRSA) are associated with higher rates of treatment failure.

Mass spectrometry studies of lycodine-type Lycopodium alkaloids: sauroxine and N-demethylsauroxine.

Rationale: Sauroxine and N-demethylsauroxine are lycodine-type Lycopodium alkaloids. In recent years, Lycopodium alkaloids have gained significant interest due to their unique skeletal characteristics as well as due to their acetylcholinesterase activity. It is known that drugs that inhibit acetylcholinesterase can be used to treat the early stages of Alzheimer's disease.

Chemistry and biological activity of coumarins at molecular level.

Synthetic coumarins were prepared in high yields using ionic liquids as an environmental friendly alternative. 3,4-Dimethyl-7-hydroxycoumarin (3ab) and 3-isopropyl-4-methyl-5,7-dihydroxycoumarin (3bc) showed interesting activity against Taq DNA polymerase with IC50 values of 115.7 microM and 82.

A new semisynthetic derivative of sauroine induces LTP in hippocampal slices and improves learning performance in the Morris Water Maze.

Two semisynthetic acetyl derivatives of the alkaloid sauroine from Huperzia saururus, monoacetyl sauroine, and diacetyl sauroine (DAS) were obtained and their chemical structures were analyzed by NMR. While monoacetyl sauroine is the typical product of acetylation, DAS is an unexpected derivative related to the keto-enol formation of sauroine. Recordings of field excitatory post-synaptic potentials from the CA1 region of rat hippocampal slices showed that only DAS acutely applied induced chemical long-term potentiation (LTP) in a dose-dependent manner with an EC50 of 1.

Antibacterial Efficacy of Dihydroxylated Chalcones in Binary and Ternary Combinations with Nalidixic Acid and Nalidix Acid-Rutin Against Escherichia coli ATCC 25 922.

In order to determine the existence of synergism, the bacteriostatic action of flavonoids against Escherichia coli ATCC 25 922 between dihydroxylated chalcones and a clinically interesting conventional antibiotic, binary combinations of 2',3-dihydroxychalcone, 2',4-dihydroxychalcone and 2',4'-dihydroxychalcone with nalidixic acid and its ternary combinations with rutin (inactive flavonoid) were assayed against this Gram negative bacterium. Using a kinetic-turbidimetric method, growth kinetics were monitored in broths containing variable amounts of dihydroxychalcone alone, combinations of dihydroxychalcone variable concentration-nalidixic acid constant concentration and dihydroxychalcone variable concentration-nalidixic acid constant concentration-rutin constant concentration, respectively. The minimum inhibitory concentrations of dihydroxychalcones alone and its binary and ternary combinations were evaluated.

Natural Sesquiterpene Lactones Induce Oxidative Stress in Leishmania mexicana.

Leishmaniasis is a worldwide parasitic disease, caused by monoflagellate parasites of the genus Leishmania. In the search for more effective agents against these parasites, the identification of molecular targets has been attempted to ensure the efficiency of drugs and to avoid collateral damages on the host's cells. In this work, we have investigated some of the mechanisms of action of a group of natural sesquiterpene lactones that are effective against Leishmania mexicana mexicana promastigotes.

Derivatives of grindelic acid: from a non-active natural diterpene to synthetic antitumor derivatives.

Using several reactions that include homologations and asymmetric epoxidations as well as Ugi and Huisgen couplings, we generated a small focused library of new derivatives from the labdane-type diterpene grindelic acid. These compounds were evaluated as cytotoxic agents against a panel of five human solid tumor cell lines (HBL-100, HeLa, SW1573, T-47D, and WiDr). The presence of the diamide functionalizations enhanced the cytotoxic effect.

Larvicidal activity of crude extracts from Larrea cuneifolia (Zygophyllaceae) and of its metabolite nordihydroguaiaretic acid against the vector Culex quinquefasciatus (Diptera: Culicidae).

Introduction: The aim of the present study was to analyze the larvicidal activity of different crude extracts of Larrea cuneifolia and its most abundant lignan, nordihydroguaiaretic acid (NDGA), against Culex quinquefasciatus.

Methods: Chloroform, methanol, and aqueous extracts from L. cuneifolia and NDGA were tested against larvae of Cx.

Cytotoxic bioactivity of some phenylpropanoic acid derivatives.

In this study, we synthesized a series of phenylpropanoic acid derivatives based on modifications at four selected points of the molecular scaffold. The in vitro antiproliferative activities of the compounds were examined in representative human solid tumor cell lines. A SAR was established pointing out the relevance of the substituents.

Sesquiterpene lactones and the diterpene 5-epi-icetexone affect the intracellular and extracellular stages of Trypanosoma cruzi.

Chagas disease is a major health problem in Latin America and is caused by the parasitic protozoan Trypanosoma cruzi. Although many drugs have been used to alleviate the disease, these have been ineffective in the chronic phase and have also presented numerous side effects on patients. In this study we tested the effect of three sesquiterpene lactones (dehydroleucodine, helenalin and mexicanin) and a diterpene (5-epi-icetexone) on parasites (Y-strain) grown in host cells.

Activation of human leukemic mast cell line LAD2 is modulated by dehydroleucodine and xanthatin.

The aim of the present study was to determine whether dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one inhibit the activation of human leukemic LAD2 mast cells induced by compound 48/80 or the calcium ionophore A23187. LAD2 cells were preincubated in the presence of test drugs and then challenged with the secretagogues. This study provides the first evidence in favor of the view that dehydroleucodine and xanthatin inhibit the degranulation of LAD2 cells, thus acting as human mast cell stabilizers.

The effect of the diterpene 5-epi-icetexone on the cell cycle of Trypanosoma cruzi.

Numerous natural compounds have been used against Trypanosoma cruzi, the causative agent of Chagas' disease. Here, we studied the effect of the diterpene 5-epi-icetexone on growth and morphology of parasites synchronized with hydroxyurea, at different periods of time after removal of the nucleotide. We observed that the diterpene does not affect the growth of the parasites when added within 10 h after removal of hydroxyurea, but the compound was effective on growth when added to the cultures after 12 h.

Antiviral effect and mode of action of methanolic extract of Verbascum thapsus L. on pseudorabies virus (strain RC/79).

The methanolic extract of Verbascum thapsus was evaluated for its antiviral activity against the pseudorabies virus strain RC/79 (PrV), and also for its cytotoxic activity on Vero cells. The extract showed CC₅₀ values of 1100 µg mL⁻¹ and 1426 µg mL⁻¹ by NRU and MTT assays, respectively. The 50% inhibitory concentration of the extract for PrV plaque formation was determined at 35 µg mL⁻¹, and selectivity indices were 31.

The effect of dehydroleucodine in adipocyte differentiation.

Dehydroleucodine (DhL) is a sesquiterpene lactone of the guaianolide group with gastric cytoprotective activity. Recent studies have also demonstrated that DhL inhibits the proliferation of vascular smooth muscle cells. In this study we examined the effect of DhL in the differentiation of 3T3-L1 preadipocytes.

Genotoxic evaluation of a methanolic extract of Verbascum thapsus using micronucleus test in mouse bone marrow.

Verbascum thapsus L. is a medicinal plant and has been used to treat numerous pulmonary diseases, asthma, inflammatory disease, spasmodic coughs and migraine headaches. Several studies have demonstrated that different extracts of V.

Coumarin metabolic routes in Aspergillus spp.

Coumarin metabolism by several Aspergillus strains was studied. Aspergillus ochraceus and Aspergillus niger carried out the reduction of the C3-C4 double bond to yield dihydrocoumarin in 24h. Meanwhile, the first strain did not transform dihydrocoumarin after 7d, A.

In silico study of the inhibition of DNA polymerase by a novel catalpol derivative.

In this work, a novel catalpol derivative (6,10,2',6'-tetraacetyl-O-catalpol), which was previously obtained by our group and shown experimentally to inhibit a type of Taq DNA polymerase, was studied in silico. Studies of the interaction of 6,10,2',6'-tetraacetyl-O-catalpol with the Klentaq fragment of the Taq DNA polymerase I from Thermus aquaticus helped to elucidate the mechanism of inhibition of the enzyme, and offered valuable information that can be used to propose substrate structural modifications aimed at increasing the binding affinity. Classical and semi-empirical methods were used to characterize the conformational preferences of this organic compound in solution.

Evaluation of antiviral activity of aqueous extracts from Achyrocline satureioides against Western equine encephalitis virus.

Achyrocline satureioides (Asteraceae) is a medicinal plant traditionally used in Argentina for the treatment of intestinal infections and various digestive disorders. Its infusion is widely utilised for respiratory problems and viral infections. The objective of this study was to investigate cytotoxicity, virucidal and antiviral properties of the cold aqueous extract (CAE) and hot aqueous extract (HAE) of this plant against Western equine encephalitis virus (WEEV).

Enhancement of antiproliferative activity by molecular simplification of catalpol.

Two iridoid scaffolds were synthesized enantioselectively using as key step an l-proline-catalyzed alpha-formyl oxidation. The in vitro antiproliferative activities were evaluated against a representative panel of human solid tumor cell lines. Both iridoids induced considerably growth inhibition in the range 0.

Tessaric acid derivatives induce G2/M cell cycle arrest in human solid tumor cell lines.

A series of analogs were synthesized in a straightforward manner from naturally available sesquiterpenes ilicic acid and tessaric acid. The in vitro antiproliferative activities were examined in the human solid tumor cell lines A2780, HBL-100, HeLa, SW1573, T-47D and WiDr. The most potent analog induced considerably growth inhibition in the range 1.

Novel anti-ulcer alpha,beta-unsaturated lactones inhibit compound 48/80-induced mast cell degranulation.

The present study was designed to examine the effects of a sesquiterpene lactone isolated from Artemisia douglasiana Besser (dehydroleucodine), a xanthanolide sesquiterpene isolated from Xanthium cavanillesii Schouw (xanthatin) and a semisynthetic butenolide (3-benzyloxymethyl-5H-furan-2-one) on mast cell degranulation induced by compound 48/80. Peritoneal mast cells from male adult Sprague-Dawley rats were purified in Percoll, preincubated in the presence of test lactones (dehydroleucodine, xanthatin or 3-benzyloxymethyl-5H-furan-2-one) and then challenged with the mast cell activator compound 48/80 (10 microg/ml). Concentration-response and kinetic studies of mast cell serotonin release evoked by compound 48/80, evaluation of mast cell viability and morphology by light and electron microscopy, and comparative studies using ketotifen and sodium chromoglycate were carried out.