The influence of thioether-substituted ligands in dicopper(II) complexes: Enhancing oxidation and biological activities.

This paper describes the synthesis, structural analysis, as well as the magnetic and spectroscopic characterizations of three new dicopper(II) complexes with dinucleating phenol-based ligands containing different thioether donor substituents: aromatic (1), aliphatic (2) or thiophene (3). Temperature-dependent magnetometry reveals the presence of antiferromagnetic coupling for 1 and 3 (J = -2.27 cm-1 and -5.01 cm-1, respectively, H = -2JS1S2) and ferromagnetic coupling for 2 (J = 5.72 cm-1). Broken symmetry DFT calculations attribute this behavior to a major contribution from the dz2 orbitals for 1 and 3, and from the dx2-y2 orbitals for 2, along with the p orbitals of the oxygens. The bioinspired catalytic activities of these complexes related to catechol oxidase were studied using 3,5-di-tert-butylcatechol as substrate. The order of catalytic rates for the substrate oxidation follows the trend 1 > 2 > 3 with kcat of (90.79 ± 2.90) × 10-3 for 1, (64.21 ± 0.99) × 10-3 for 2 and (14.20 ± 0.32) × 10-3 s-1 for 3. The complexes also cleave DNA through an oxidative mechanism with minor-groove preference, as indicated by experimental and molecular docking assays. Antimicrobial potential of these highly active complexes has shown that 3 inhibits both Staphylococcus aureus bacterium and Epidermophyton floccosum fungus. Notably, the complexes were found to be nontoxic to normal cells but exhibited cytotoxicity against epidermoid carcinoma cells, surpassing the activity of the metallodrug cisplatin. This research shows the multifaceted properties of these complexes, making them promising candidates for various applications in catalysis, nucleic acids research, and antimicrobial activities.

Antiulcer mechanisms of the hydroalcoholic extract from Aztec marigolds' medicinal and edible flowers (Tagetes erecta L.).

The antiulcer mechanisms of the dry extract of T. erecta flowers (DETe) were studied here. The acute ulcers induced by acidified ethanol or indomethacin were reproduced in mice pretreated with DETe (3 - 300 mg/kg). The antiulcer activity of DETe was also verified in mice pretreated with NEM, L-NAME, indomethacin, or yohimbine. The antisecretory effect of DETe was verified in rats, and its anti-Helicobacter pylori activity was determined in vitro. DETe (300 mg/kg, p.o) reduced the ethanol- or indomethacin-induced ulcer by 49 and 93%, respectively. The pre-treatment with L-NAME, NEM or yohimbine abolished the gastroprotective effect of DETe. However, DETe did not change the volume, acidity, or peptic activity in rats and did not affect H. pylori. This study expands knowledge about the antiulcerogenic potential of DETe, evidencing the role of nitric oxide, non-protein sulfhydryl groups, α2 adrenergic receptors, and prostaglandins, but not antisecretory or anti-H. pylori properties.

Novel one-pot synthesis of a library of 2-aryloxy-1,4-naphthoquinone derivatives. Determination of antifungal and antibacterial activity.

The development of new antibiotics and inexpensive antifungals is an important field of research. Based on the privileged pharmacophore of lawsone, a series of phenolic ether derivatives of 1,4-naphthoquinone were synthesized easily in one step in reasonable yields. All the new compounds were characterized and tested as potential antifungal and antibacterial agents against Candida albicans, Escherichia coli and Staphylococcus aureus. Compound 55 has significant antibacterial action (as good as or better than the controls) against E. coli and S. aureus. Against C. albicans, compounds 38, 46, 47 and 60 were the best candidates as antifungals. Using a qualitative structure-activity analysis, a correlation between molar mass and antimicrobial activity was identified, regardless of the substituent group on the phenolic moiety, except for 55 and 63, where electronic effects seem more important. An in silico evaluation of the absorption, distribution, metabolism and excretion (ADME) for 37, 50, 55 and 63 was made, indicating that the classic Lipinski's rule of five applies in all cases.

Preparations from Campomanesia reitziana reduce the gastrointestinal motility and castor oil-induced diarrhea in a non-opioid and non-dopaminergic pathway in mice and display antimicrobial activity in vitro.

BACKGROUND: This study investigated the antidiarrheal potential of the aqueous extract (AECR) and hydroalcoholic extract of Campomanesia reitziana leaves (HECR), its ethyl acetate (EAF) and dichloromethane fractions (DCMF), and myricitrin isolated from EAF. METHODS: The total phenols and flavonoids were measured, followed by chromatography and myricitrin isolation. The 2,2-diphenyl-1-picryl-hydrazyl scavenger activity, the cytotoxicity, and the effects on LPS-induced nitrite production in intestinal epithelial cells (IEC-6) were quantified. The effect of HECR, EAF, DCMF, and AECR on intestinal motility (IT), gastric emptying (GE), and castor oil-induced diarrhea in mice was determined, as well as its antimicrobial activity. KEY RESULTS: The administration of AECR 10% (10 ml/kg, p.o), but not HECR (300 mg/kg), reduced the GE and IT by 52 and 51%. The EAF and DCMF at 300 mg/kg also reduced IT but did not change GE. Moreover, AECR and EAF, but not DCMF, inhibited the castor oil-induced diarrhea and naloxone or metoclopramide pretreatment did not change these effects. Myricitrin did not change IT and the evacuation index of mice. Finally, the dry residue of AECR inhibited bacterial growth and EAF showed bacteriostatic activity against S. aureus, E. coli, and S. typhimurium and antifungal for C. albicans. However, none of the preparations alter the viability of Giardia spp. trophozoites. CONCLUSIONS: The AECR and EAF can be effective to treat diarrhea acting through opioid- or dopaminergic type 2 receptor-independent mechanisms and by its antimicrobial actions.

Improvement in phloroglucinol compound extracted from different parts of Eugenia umbelliflora monitored by LC-UV and antimicrobial activity.

The phloroglucinol eugenial C, eugenial D and eugenial E are the main active compounds in Eugenia umbelliflora fruits. This study aims to evaluate the extraction conditions of E. umbelliflora, using ethanol as solvent, focusing on the phloroglucinol and antimicrobial activity. In order to optimize the extraction conditions, ethanol 50, 70 and 90 oGL was used as a solvent in the proportions of 1:20 (w/v) of drug:solvent ratio (D:S), stirring (330 rpm) at room temperature during 4 h, monitored by LC-UV and antimicrobial assay. The LC-UV method developed was linear over a concentration range of 3.4-68.0, 5.3-106.0 and 5.0-100.8 µg.mL-1 of eugenial C, eugenial D and eugenial E, having LOQ of 1.68, 1.33 and 0.8 µg.mL-1, respectively. The fruits showed the best herbal raw material and showed the highest phloroglucinol concentration and activity against S. aureus, when extracted with ethanol 90oGL, during 4 h, at 1:20 of D:S.

Synthesis of Ag@Fe2O3 nanocomposite based on O-carboxymethylchitosan with antimicrobial activity.

In this paper, nano-hybrid particles of Ag@Fe2O3 based on O-carboxymethylchitosan were successfully synthesized using different reducing agents (NaBH4, sucrose) and without reducing agent. The smallest silver nanoparticles were those prepared without reducing agent (∼5±3nm). The average size of silver particles prepared with NaBH4 is around 5-15nm, and for samples prepared with sucrose, the average particle size is 10-25nm. The magnetization curves are roughly reversible, indicating that γ-Fe2O3 nanoparticles transit to a superparamagnetic state. Nanocomposites subjected to antimicrobial tests showed great antimicrobial activity against gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria, and good activity against the yeast Candida albicans and resistant strains of Staphylococcus aureus. The antibacterial behavior as a function of time was investigated in microbial growth kinetics, and the best nanocomposite was the one without reducing agent, which completely inhibited microbial growth for 48h.

Role of gastric mucus secretion, oxinitrergic system and sulfhydryl groups on the gastroprotection elicited by Polygala cyparissias (Polygalaceae) in mice.

OBJECTIVES: This study has aimed to assess the mechanisms of action for the gastroprotective effect of the acetone extract (PCAE) and methanol fraction (PCMF) of Polygala cyparissias, as well as to evaluate the activity of 1,3,6,8-tetrahydroxy-2,7-dimethoxyxanthone (1), 1,7-dihydroxy-2,3-dimethoxyxanthone (2) and astragalin (3). METHODS: Gastric secretion and mucus content were determined by pylorus ligation in mice. Nitric oxide (NO) and sulfhydryl group participation were observed by the pretreatment of mice with L-NAME or NEM. Acute ulcer was induced by ethanol/HCl and chronic ulcer by acetic acid. Anti-Helicobacter pylori activity was evaluated by the agar solid dilution assay. KEY FINDINGS: Neither PCAE nor PCMF had the ability to reduce H(+) concentration. However, both of them enhanced mucus secretion. PCAE demonstrated its gastroprotection in a NO-dependent manner, while PCMF exerted the activity depending on the sulfhydryl group. In chronic ulcer, the curative ratios for the PCAE and PCMF were 67.5 and 58.4%, respectively. No effect over H. pylori was detected. Compounds 1, 2 and 3 were able to reduce lesions in the order of 79.6, 73.8 and 67.6%, respectively. CONCLUSIONS: The data suggested that PCAE and PCMF displayed antiulcer activity due to different mechanisms and with the participation of phenolic compounds obtained from the plant.

Synthesis and biological evaluation of N-antipyrine-4-substituted amino-3-chloromaleimide derivatives.

This paper describes the synthesis of new cyclic imides obtained by reaction with N-antipyrine-3,4-dichloromaleimides and different aromatic amines. The analgesic activity of the synthesized compounds was initially investigated against the writhing test in mice, followed by analysis of the most promising compounds in this model and in the formalin-induced model. The results indicate that the compounds containing the electron-withdrawing substituents in the para position of the substitute ring exerted more potent analgesic activity in mice, being much more potent than the prototype N-antipyrine-3,4-dichloromaleimide and some reference drugs. Some compounds exhibited activity against human opportunistic and pathogenic fungi, with MIC values of between 40 and 100 µg/mL (91.74 and 236.96 µM), and it was verified that only a few compounds presented potential for cytotoxic activity.

Evaluation of antifungal activity of Piper solmsianum C. DC. var. solmsianum (Piperaceae).

We have studied the crude methanolic extract (CME), some fractions (hexane, dichloromethane and ethyl acetate) and four pure compounds: eupomatenoid-3 (1), eupomatenoid-5 (2), conocarpan (3) and orientin (4), from Piper solmsianum, for possible antifungal activity against 12 pathogenic fungi. The minimal inhibitory concentration (MIC) was determined and the experiments showed that the CME exhibited antifungal action against all the dermatophytes tested, with MIC values of between 20 microg/ml to 60 microg/ml. Similar activity also was verified for the hexane, dichloromethane and ethyl acetate fractions. However, the starting material (CME), and all the fractions, did not exert inhibitory effect against hyaline hyphomycetes and were only discretely active against the zigomycetes and yeasts. Compounds 2, 3 and 4 also exhibited pronounced activity against all the dermatophytes tested (MIC< or =1 to 9 microg/ml) with potency as high as the standard antifungal drug (ketoconazole). Compound 3 also exhibited activity against all the yeasts tested. In conclusion, the antifungal activity of P. solmsianum seems to be related mainly to the presence of compounds 2, 3 (neolignans) and 4 (flavonoid), however it was verified that another active compound, as yet unidentified, exists in the plant.