Effect of 2-chloro-N-(4-fluoro-3-nitrophenyl)acetamide in combination with antibacterial drugs against Klebsiella pneumoniae.

Klebsiella pneumoniae is a species of Gram-negative bacteria related to a wide range of infections and high rates of drug resistance. The combined use of antibacterial agents is one of the strategies that has been analyzed in recent years as part of the alternatives in the treatment of drug-resistant infections. Recently, the antibacterial activity of of 2-chloro-N-(4-fluoro-3-nitrophenyl)acetamide has been demonstrated against K. pneumoniae, also indicating that this acetamide did not show significant cytotoxic potential in preliminary tests. Thus, it becomes an interesting substance for future studies that explore its antimicrobial capacity, including investigating its association with antibacterial drugs. Based on this, this research aimed to analyze the effects of the association of 2-chloro-N-(4-fluoro-3-nitrophenyl)acetamide (CFA) with ciprofloxacin, cefepime, ceftazidime, meropenem and imipenem against K. pneumoniae strains. The results showed additivity when the substance was combined with ciprofloxacin and cefepime, indifference when associated with ceftazidime and synergistic effect when combined with meropenem and imipenem. Thus, the acetamide was able to optimize the effects of antibacterial drugs, reducing the concentrations necessary to cause bacterial death. These data indicate a potential future clinical use of these combinations, and further studies are needed to analyze this viability.

Morita-Baylis-Hillman adducts derived from thymol: synthesis, in silico studies and biological activity against Giardia lamblia.

Giardiasis is a neglected disease, and there is a need for new molecules with less side effects and better activity against resistant strains. This work describes the evaluation of the giardicidal activity of thymol derivatives produced from the Morita-Baylis-Hillman reaction. Thymol acrylate was reacted with different aromatic aldehydes, using 1,4-diazabicyclo[2.2.2]octane (DABCO) as a catalyst. Eleven adducts (8 of them unpublished) with yields between 58 and 80% were obtained from this reaction, which were adequately characterized. The in silico prediction showed theoretical bioavailability after oral administration as well as antiparasitic activity against Giardia lamblia. Compound 4 showed better biological activity against G. lamblia. In addition to presenting antigiardial activity 24 times better than thymol, this MBHA was obtained in a short reaction time (3 h) with a yield (80%) superior to the other investigated molecules. The molecule was more active than the precursors (thymol and MBHA 12) and did not show cytotoxicity against HEK-293 or HT-29 cells. In conclusion, this study presents a new class of drugs with better antigiardial activity in relation to thymol, acting as a basis for the synthesis of new bioactive molecules. Molecular hybridization technique combined with the Morita-Baylis-Hillman reaction provided new thymol derivatives with giardicidal activity superior to the precursor molecules.

First complete NMR data and theoretical study of an antimicrobial formylated dihydrochalcone from Psidium guineense Sw.

Chalcones are a widespread group of natural compounds characterized by the basic structure 1,3-diaryl-2-propen-1-one. In this study, we focused on the uncommon formylated chalcone 3'-formyl-2',4',6'-trihydroxy-5'-methyldihydrochalcone that possess interesting antimicrobial and anticancer potential. Considering the pharmacological relevance of this compound, we report its isolation and the first complete and unequivocal NMR data for this substance, corroborated by in silico theoretical study. In addition to that, its antibacterial potential was evaluated and the compound presented strong activity against Pseudomonas aeruginosa.[Formula: see text].

Vasorelaxation, induced by Dictyota pulchella (Dictyotaceae), a brown alga, is mediated via inhibition of calcium influx in rats.

This study aimed to investigate the cardiovascular effects elicited by Dictyota pulchella, a brown alga, using in vivo and in vitro approaches. In normotensive conscious rats, CH(2)Cl(2)/MeOH Extract (CME, 5, 10, 20 and 40 mg/kg) from Dictyota pulchella produced dose-dependent hypotension (-4 ± 1; -8 ± 2; -53 ± 8 and -63 ± 3 mmHg) and bradycardia (-8 ± 6; -17 ± 11; -257 ± 36 and -285 ± 27 b.p.m.). In addition, CME and Hexane/EtOAc Phase (HEP) (0.01-300 µg/mL) from Dictyota pulchella induced a concentration-dependent relaxation in phenylephrine (Phe, 1 µM)-pre-contracted mesenteric artery rings. The vasorelaxant effect was not modified by the removal of the vascular endothelium or pre-incubation with KCl (20 mM), tetraethylammonium (TEA, 3 mM) or tromboxane A(2) agonist U-46619 (100 nM). Furthermore, CME and HEP reversed CaCl(2)-induced vascular contractions. These results suggest that both CME and HEP act on the voltage-operated calcium channel in order to produce vasorelaxation. In addition, CME induced vasodilatation after the vessels have been pre-contracted with L-type Ca(2+) channel agonist (Bay K 8644, 200 nM). Taken together, our data show that CME induces hypotension and bradycardia in vivo and that both CME and HEP induce endothelium-independent vasodilatation in vitro that seems to involve the inhibition of the Ca(2+) influx through blockade of voltage-operated calcium channels.

Araçain, a tyrosol derivative and other phytochemicals from Psidium guineense Sw.

Psidium guineense Sw. (Myrtaceae) is a shrub distributed all over South America and Brazil. Its leaves are traditionally used to treat digestive problems and infections. Several biological activities have been reported for P. guineense extracts, however phytochemical studies are scarce. The present study is on the isolation of compounds from P. guineense leaf extracts using chromatographic and spectroscopic techniques and evaluation of their antibacterial activity. Araçain, a tyrosol derivative was isolated as a natural product for the first time. Other compounds isolated were ursolic acid, a phaeophorbide and three flavonoids. The extracts were tested for their antimicrobial activity against Klebsiella pneumoniae strains and they showed moderate to high antibacterial activity.