Marcia Paranho Veloso

Antimicrobial activity of benzophenones and extracts from the fruits of Garcinia brasiliensis.

The pericarp and seeds from fruits of Garcinia brasiliensis were subjected to extraction with hexane and ethanol. The pericarp hexane extract (PHE) and seed ethanol extract (SEE) were purified by silica gel column chromatography, which permitted isolation of the prenylated benzophenones 7-epiclusianone (1) and guttiferone-A (2), respectively. The antimicrobial activity of PHE, SEE, and compounds 1 and 2 were evaluated against Candida albicans, Staphylococcus aureus, Escherichia coli, and Bacillus cereus cultures. The minimum inhibitory concentration and minimum bactericidal concentration were established. The substances presented activity against S. aureus and B. cereus as follows: PHE, 4.0 microg/mL and 2.4 microg/mL; SEE, 10.0 microg/mL and 12.6 microg/mL; 7-epiclusianone, 1.2 microg/mL and 0.6 microg/mL; and guttiferone-A, 2.4 microg/mL and 2.4 microg/mL, respectively. The direct relationship between the lipophilic character of the structure and activity in Gram-positive bacteria was specifically observed. Therefore these extracts and prenylated benzophenones represent an interesting topic for further studies and open possibilities for an alternative control of diseases associated with Gram-positive bacteria.

Complete assignment of the 1H and 13C NMR spectra of garciniaphenone and keto-enol equilibrium statements for prenylated benzophenones.

This article reports the structural elucidation by IR, UV and MS spectroscopic data along with 1H and 13C NMR chemical shift assignments of two benzophenones isolated from the fruit pericarp of Garcinia brasiliensis Mart. (Clusiaceae): garciniaphenone, (1R,5S,7S)‐3‐benzoyl‐4‐hydroxy‐6,6‐dimethyl‐5,7‐di(3‐methyl‐2‐butenyl)bicyclo[3.3.1]non‐3‐ene‐2,9‐dione, a novel triprenylated benzophenone; and 7‐epi‐clusianone, a tetraprenylated benzophenone that has already been extracted from another species of the same family. Furthermore, the keto‐enol tautomeric equilibrium at solution‐state was described for these compounds by 1D and 2D NMR spectral methods and one attempt to rationalize the different ratios between the noted tautomers was based on stereochemical features. Copyright

Natural Polyprenylated Benzophenones: Keto-Enol Tautomerism and Stereochemistry

The keto-enol tautomerism and stereochemistry study of a HIV-inhibitory natural benzophenone, (1R,5R,7R,8S)-(+)-3-(10-(3,4-dihydroxyphenyl)-10-hydroxymethylene)-8-methyl -1,5,7-tris(3-methyl-2-butenyl)-8-(4-methyl-3-pentenyl)-bicyclo[3.3.1]nonane-2,4,9-trione (a), isolated from Garcinia brasiliensis seeds is presented. The crystal structure of (a), which is also know as guttiferona A, was determined by X-ray diffraction and its intra and inter-molecular geometries discussed and compared with two analogue natural benzophenones: clusianone and epiclusianone. In (a), the hydroxyl H atom from enolizable 2,4,10-trione moiety is linked in the oxygen atom bonded to 10-(3,4-dihydroxyphenyl)methylene group, in opposition to the related natural benzophenones, where this analogue H-atom is placed in different O-atoms from bicyclo[3.3.1]nonane ring system. Such behaviour can be explained by the presence of aromatic OH6 group in (a) that origins a further delocalized resonance path along of 3,4-dihydroxyphenyl-C10-OH2 group. In addition, the (a) stereochemistry around C7 atom is compared with known structures of clusianone and epiclusianone and the influence from configuration in this chiral C-atom to structural features found in the enolizable system is proposed.

Synthesis and Biological Evaluation of New Eugenol Mannich Bases as Promising Antifungal Agents

New Mannich base‐type eugenol derivatives were synthesized and evaluated for their anticandidal activity using a broth microdilution assay. Among the synthesized compounds, 4‐allyl‐2‐methoxy‐6‐(morpholin‐4‐ylmethyl) phenyl benzoate (7) and 4‐{5‐allyl‐2‐[(4‐chlorobenzoyl)oxy]‐3‐methoxybenzyl}morpholin‐4‐ium chloride (8) were found to be the most effective antifungal compounds with low IC50 values, some of them well below those of reference drug fluconazole. The most significant IC50 values were those of 7 against C. glabrata (1.23 μm), C. albicans and C. krusei (both 0.63 μm). Additionally, the synthesized compounds were evaluated for their in vitro cytotoxic effects on human mononuclear cells. As result, the cytotoxic activity of eugenol in eukaryotic cells decreased with the introduction of the morpholinyl group. Given these findings, we point out compounds 7 and 8 as the most promising derivatives because they showed potency values greater than those of eugenol and fluconazole and they also presented high selectivity indexes.

Synthesis and antimicrobial activity of 6-triazolo-6-deoxy eugenol glucosides.

A new series of 1,2,3-triazole eugenol glucosides were synthesized. The new compound structures were confirmed by MS, (1)H NMR and (13)C NMR. All of the synthesized compounds were screened for antimicrobial and cytotoxic activity. Five compounds exerted significant activity against the Gram-negative bacteria Salmonella typhimurium with low IC50 values (49.73-68.53 μΜ), and seven compounds were active against the Gram-positive bacteria Micrococcus luteus (42.89-210.94 μM). In vitro cytotoxicity on mouse spleen cells was also evaluated. One compound bearing a phenyl substituent at the triazole ring showed good activity against Salmonella typhimurium (49.73 μM) and low toxicity to normal cells (CC50=157.83 μM). Thus, the compounds herein can be considered for further modification for improving their antibacterial activity or obtaining novel antibacterial drug candidates.

Methyl 4-(piperidin-1-ylcarbon­yl)benzoate

In the title compound, C14H17NO3, the piperidine ring has a chair conformation and an intramolecular C—H⋯O interaction stabilizes the molecular conformation. In the crystal, weak intermolecular C—H⋯O interactions occur.

New Eugenol Glucoside-based Derivative Shows Fungistatic and Fungicidal Activity against Opportunistic Candida glabrata.

A new series of glucosides modified in their saccharide units were synthesized, evaluated against Candida sp., and compared to prototype 1, an eugenol tetracetyl glucoside previously synthesized and shown to be active against Candida glabrata. Among the new glucosides, benzyl derivative 5 was the most promising, showing fungistatic activity at IC50 18.1 μm against Candida glabrata (threefold higher than fluconazole) and fungicidal activity with a low IC90 value of 36.2 μm. Moreover, the cytotoxic activity of compound 5 (CC50: 580.9 μm), tested in peripheral blood mononuclear cells, suggests its potential as an agent to treat Candida glabrata infections, with a selectivity index of 32. The new eugenol glucoside 5 may be considered as a novel structural pattern in the development of new anti‐Candida drugs.

Synthesis and characterization of the atropisomeric relationships of a substituted N‐phenyl‐bipyrazole derivative with anti‐inflammatory properties

This work describes the atropisomeric relationships of 3-methyl-5-(3-methyl-5-phenyl-1H-pyrazol-1-yl)-1-phenyl-1H-pyrazol-4-amine (2d), which belongs to series 4-aminobipyrazole derivatives designed as anti-inflammatory agents. The (1)H nuclear magnetic resonance spectra obtained in the presence of a chiral lanthanide shift salt associated to chiral high-performance liquid chromatography analysis, X-ray diffraction, and molecular modeling tools confirmed that ortho bis-functionalized bipyrazole 2d exists as a mixture of aR,aS-atropisomers. These results provide useful information to understand the pharmacological profile of this derivative and of other 4-aminobipyrazole analogs.

Relevance of Trypanothione Reductase Inhibitors on Trypanosoma cruzi Infection: A Systematic Review, Meta-Analysis, and In Silico Integrated Approach

Due to the rudimentary antioxidant defenses in Trypanosoma cruzi, disruptors of redox balance are promising candidates for new antitrypanosomal drugs. We developed an integrated model based on systematic review, meta-analyses, and molecular modeling to evaluate the effect of trypanothione reductase (TR) inhibitors in T. cruzi infections. Our findings indicated that the TR inhibitors analyzed were effective in reducing parasitemia and mortality due to Trypanosoma cruzi infection in animal models. The most investigated drugs (clomipramine and thioridazine) showed no beneficial effects on the occurrence of infection-related electrocardiographic abnormalities or the affinity and density of cardiac β-adrenergic receptors. The affinity between the tested ligands and the active site of TR was confirmed by molecular docking. However, the molecular affinity score was unable to explain TR inhibition and T. cruzi death in vitro or the antiparasitic potential of these drugs when tested in preclinical models of T. cruzi infection. The divergence of in silico, in vitro, and in vivo findings indicated that the anti-T. cruzi effects of the analyzed drugs were not restricted to TR inhibition. As in vivo studies on TR inhibitors are still scarce and exhibit methodological limitations, mechanistic and highly controlled studies are required to improve the quality of evidence.

Extruded sorghum (Sorghum bicolor L.) reduces metabolic risk of hepatic steatosis in obese rats consuming a high fat diet

The study investigated the effect of extruded sorghum flour (ESF) in a high fat diet (HFD) on biometric measurements and hepatic lipogenesis. Male Wistar rats were fed a normal diet (AIN-93M), HFD, HFD plus ESF replacing 50% cellulose and 100% corn starch (HFDS50), or HFD plus ESF replacing 100% cellulose and 100% corn starch (HFDS100) for eight weeks. ESF reduced the body mass index and liver weight of obese rats. Additionally, ESF reduced hepatic lipogenesis by increasing adiponectin 2 receptor gene expression and gene and protein expressions of peroxisome proliferator-activated receptor α (PPARα), while reducing the gene expression of sterol regulatory element-binding transcription factor 1. Molecular docking analysis revealed the affinity of ESF compounds (luteolinidin, apigeninidin, 5-methoxy-luteolinidin, and 7-methoxy-apigeninidin) with the PPAR-α receptor. Histological analysis confirmed the decreased grade of hepatic steatosis in obese rats. These data indicate the potential of ESF to reduce metabolic risk of hepatic steatosis associated with lipogenesis and obesity.