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1.
Chem Biodivers ; : e202400786, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38777789

ABSTRACT

This study carried out to investigate the anti-inflammatory and antinociceptive effect of tropane alkaloid (EB7) isolated from E. bezerrae. It evaluated the toxicity and possible involvement of ion channels in the antinociceptive effect of EB7, as well as its anti-inflammatory effect in adult zebrafish (Zfa). Docking studies with EB7 and COX-1 and 2 were also performed. The tested doses of EB7 (4, 20 and 40 mg/kg) did not show any toxic effect on Zfa during the 96h of analysis (LD50>40 mg/kg). They did not produce any alteration in the locomotor behavior of the animals. Furthermore, EB7 showed promising pharmacological effects as it prevented the nociceptive behavior induced by hypertonic saline, capsaicin, formalin and acid saline. EB7 had its analgesic effect blocked by amiloride involving the neuromodulation of ASICs in Zfa. In evaluating the anti-inflammatory activity, the edema induced by κ-carrageenan 3.5 % was reduced by the dose of 40 mg/kg of EB7 observed after the fourth hour of analysis, indicating an effect similar to that of ibuprofen. Molecular docking results indicated that EB7 exhibited better affinity energy when compared to ibuprofen control against the two evaluated targets binding at different sites in the cocrystallized COX-1 and 2 inhibitors.

2.
Chem Biodivers ; 21(7): e202301771, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38628065

ABSTRACT

The crude acetone extract of a marine Micromonospora sp. strain associated with Eudistoma vannnamei was fractioned with hexane and ethyl acetate. The crude extract and both soluble fractions were assayed against several bacteria strains. The new polycyclic quinones 12-hydroxy-9-propyltetracene-6,1-dione (1), 5,12-dihydroxy-4-methoxy-9-propyltetracene-5,12-dione (2), and 4,6-dihydroxy-3-methoxycarbonyl- methyl-6a-(oxobutyl)-5,12-anthraquinone (3), along with the known 4,6-dihydroxy-3-methoxycarbonyl-methyl-6a-(oxo-3-methyl-butyl)-5,12-anthraquinone (4) and 4,6-dihydroxy-3-methoxycarbonyl-methyl-6a-(oxopentyl)-5,12-anthraquinone (5) were isolated from the hexane-soluble fraction, while from the active ethyl acetate fraction were isolated the known 4,6,11-trihydroxy-9-propyltetracene-5,12-dione (6), 4-methoxy-9-propyltetracene-6,11-dione (7), 7,8,9,10-tetrahydro-9-hydroxy-4-methoxy-9-propyltetracene-6,11-dione (8), and 10ß-carbomethoxy-7,8,9,10-tetrahydro-4,6,7α,9α,11-pentahydroxy-9-propyltetracene-5,12-dione (9). The structures of the new compounds were established by interpretation of HRMS and NMR techniques. A study of molecular docking was performed with the compounds from the active ethyl acetate fraction to correlate tentatively with the antimicrobial activity. Molecular docking, RMSD, RMSF, and MM-GBSA evaluations were performed to investigate the inhibitory activity of 6-8 against the protein PDB-codex 1MWT, being considered a promising target for studying drug development responsible for inhibiting replication of Staphylococcus aureus. Penicillin G was used as the standard inhibitory. Anthracyclinones 6-8 were the best hydrolase inhibitor with affinity energy -8.1 to -7.9 kcal/mol compared to penicillin G, which presented -6.9 kcal/mol. Both 8 and 7 present potent inhibitory effects against hydrolase through molecular dynamics simulation and exhibit favorable drug-like properties, promising new hydrolase blockers to fight bacterial infections from Staphylococcus aureus.


Subject(s)
Anti-Bacterial Agents , Microbial Sensitivity Tests , Micromonospora , Molecular Docking Simulation , Quinones , Micromonospora/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Quinones/chemistry , Quinones/pharmacology , Quinones/isolation & purification , Molecular Structure , Polycyclic Compounds/pharmacology , Polycyclic Compounds/chemistry , Polycyclic Compounds/isolation & purification
3.
Chem Biodivers ; 21(3): e202302122, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38354224

ABSTRACT

Griffinia gardneriana Ravenna, Griffinia liboniana Morren and Griffinia nocturna Ravenna (Amarillydaceae) are bulbous plants found in tropical regions of Brazil. Our work aimed to determine the alkaloid profiles of Griffinia spp. and evaluate their anxiolytic potential through in vivo and in silico assays. The plants grown in greenhouses were dried and their ground bulbs were subjected to liquid-liquid partitions, resulting in alkaloid fractions that were analyzed by gas chromatography coupled to mass spectrometry (GC-MS). Anxiolytic activity was evaluated in zebrafish (Danio rerio) through intraperitoneal injection at doses of 40, 100 and 200 mg/kg in light-dark box test. GC-MS analyses revealed 23 alkaloids belonging to different skeleton types: lycorine, homolychorine, galanthamine, crinine, haemanthamine, montanine and narcisclasine. The chemical profiles were relatively similar, presenting 8 alkaloids common to the three species. The major component for G. gardneriana and G. liboniana was lycorine, while G. nocturna consisted mainly of anhydrolycorine. All three alkaloid fractions demonstrated anxiolytic effect. Furthermore, pre-treatment with diazepam and pizotifen drugs was able to reverse the anxiolytic action, indicating involving the GABAergic and serotonergic receptors. Molecular docking showed that the compounds vittatine, lycorine and 11,12-dehydro-2-methoxyassoanine had high affinity with both receptors, suggesting them to be responsible for the anxiolytic effect.


Subject(s)
Alkaloids , Amaryllidaceae Alkaloids , Amaryllidaceae , Anti-Anxiety Agents , Phenanthridines , Animals , Amaryllidaceae/chemistry , Zebrafish , Anti-Anxiety Agents/pharmacology , Molecular Docking Simulation , Gas Chromatography-Mass Spectrometry/methods , Amaryllidaceae Alkaloids/pharmacology , Amaryllidaceae Alkaloids/chemistry , Alkaloids/pharmacology , Alkaloids/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry
4.
Chem Biodivers ; 21(4): e202400063, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38329295

ABSTRACT

The xanthone lichenxanthone did not show toxic effects (LC50>1.0 mg/mL). lichenxanthone prevented nociceptive behavior induced by acidic saline, and its analgesic effect was blocked by amiloride, highlighting the involvement of neuromodulation of acid-sensitive ion channels (ASICs). In the analysis of anti-inflammatory activity, concentrations of 0.1 and 0.5 mg/mL of lichenxanthone reduced the edema induced by k-carrageenan 3.5 %, observed from the fourth hour of analysis. This effect was similar to that observed with ibuprofen (positive control). No leukocyte infiltrates were observed in lichenxanthone, suggesting that the compound acts in the acute inflammatory response. The results of the molecular docking study revealed that lichenxanthone exhibited better affinity energy when compared to the ibuprofen control against the two targets evaluated.


Subject(s)
Ibuprofen , Zebrafish , Animals , Molecular Docking Simulation , Anti-Inflammatory Agents/pharmacology , Ion Channels
5.
Mar Drugs ; 12(12): 5839-55, 2014 Dec 04.
Article in English | MEDLINE | ID: mdl-25486109

ABSTRACT

The present study highlights the biological effects of chromomycin A2 toward metastatic melanoma cells in culture. Besides chromomycin A2, chromomycin A3 and demethylchromomycin A2 were also identified from the extract derived from Streptomyces sp., recovered from Paracuru Beach, located in the northeast region of Brazil. The cytotoxic activity of chromomycin A2 was evaluated across a panel of human tumor cell lines, which found IC50 values in the nM-range for exposures of 48 and 72 h. MALME-3M, a metastatic melanoma cell line, showed the highest sensitivity to chromomycin A2 after 48h incubation, and was chosen as a model to investigate this potent cytotoxic effect. Treatment with chromomycin A2 at 30 nM reduced cell proliferation, but had no significant effect upon cell viability. Additionally, chromomycin A2 induced accumulation of cells in G0/G1 phase of the cell cycle, with consequent reduction of S and G2/M and unbalanced expression of cyclins. Chromomycin A2 treated cells depicted several cellular fragments resembling autophagosomes and increased expression of proteins LC3-A and LC3-B. Moreover, exposure to chromomycin A2 also induced the appearance of acidic vacuolar organelles in treated cells. These features combined are suggestive of the induction of autophagy promoted by chromomycin A2, a feature not previously described for chromomycins.


Subject(s)
Autophagy/drug effects , Melanoma/drug therapy , Plicamycin/analogs & derivatives , Brazil , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Chromomycin A3/metabolism , Chromomycins/pharmacology , HCT116 Cells , HL-60 Cells , Humans , Melanoma/metabolism , Microtubule-Associated Proteins/metabolism , Plicamycin/pharmacology , Streptomyces/chemistry
6.
Phytomedicine ; 14(9): 605-12, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17399971

ABSTRACT

In the present work, we studied the effects of piplartine (PIP), an amide alkaloid isolated from the roots of Piper tuberculatum (Piperaceae), in the elevated plus maze, open field, rota rod, pentylenetetrazole (PTZ)-induced seizures, and forced swimming tests, in mice (Swiss, male, 25 g) to assess anxiolytic, sedative, muscle relaxant, anticonvulsant and antidepressant effects, respectively. Results showed that PIP (50 and 100 mg/kg, i.p.), similarly to diazepam, significantly increased not only the number of entrances (100% and 66%, respectively) but also the time of permanence in the open arms (104% and 199%, respectively), indicating that PIP presents an anxiolytic activity. Both effects were completely blocked by the previous administration of flumazenil what suggests the involvement of benzodiazepine type receptors. In the open field test, although PIP did not alter the number of crossings, it significantly increased grooming (103% and 119%) and rearing (60% and 23%), at the doses of 50 and 100 mg/kg respectively, as compared to controls. However, in the rota rod test, PIP was devoid of effect. Although in the PTZ-induced convulsion test, PIP did not alter the latency time for the onset of the first convulsion, as compared to controls, it significantly reduced in 58% and 60%, respectively, the animal's latency time to death. Furthermore, a significant and dose-dependent decrease in the immobility time, as evaluated by the forced swimming test, was observed after PIP administration (41% and 75% decrease, at the doses of 50 and 100 mg/kg, respectively), suggesting an antidepressant effect, similarly to that observed with imipramine, a classical antidepressant drug used as standard. In conclusion, we showed that PIP presents significant anxiolytic and antidepressant activities, making this drug potentially useful in anxiety and depression.


Subject(s)
Anti-Anxiety Agents/pharmacology , Antidepressive Agents/pharmacology , Behavior, Animal/drug effects , Maze Learning/drug effects , Phytotherapy , Piper , Piperidones/pharmacology , Seizures/prevention & control , Alkaloids/administration & dosage , Alkaloids/pharmacology , Alkaloids/therapeutic use , Animals , Anti-Anxiety Agents/administration & dosage , Anti-Anxiety Agents/therapeutic use , Antidepressive Agents/administration & dosage , Antidepressive Agents/therapeutic use , Dose-Response Relationship, Drug , Injections, Intraperitoneal , Male , Mice , Pentylenetetrazole , Piperidones/administration & dosage , Piperidones/therapeutic use , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Roots , Seizures/chemically induced
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