Anxiolytic-Like Action of Selected 4-(Alkylamino)-3-nitrocoumarin Derivatives in BALB/c Mice.

In this work, we explored the possible polypharmacological potential of the already established antimicrobials against gastrointestinal pathogens, 4-(alkylamino)-3-nitrocoumarins, as antianxiety agents, using a battery of in vivo experiments. Three chosen coumarin derivatives, differing in the substituent (sec-butylamino, hexadecylamino, or benzylamino) at position 4, at the doses of 25, 50 and 100 mg kg-1 , were evaluated in light/dark, open-field, horizontal wire and diazepam-induced sleep models using male BALB/c mice. Depending on the applied dose, all three tested coumarins displayed a noteworthy anxiolytic-like effect. 4-(sec-Butylamino)-3-nitro-2H-chromen-2-one and 4-(hexadecylamino)-3-nitro-2H-chromen-2-one could be recognized as true anxiolytics in the lowest applied dose, based on three tests, without exerting any sedative effects. Thus, the 3-nitrocoumarin core deserves further chemical diversity exploration in the 'antianxiety' direction.

A new longipinane ketone from Achillea abrotanoides (Vis.) Vis.: chemical transformation of the essential oil enables the identification of a minor constituent.

INTRODUCTION: Minor plant constituents are difficult to identify due to the challenging isolation and acquiring of reliable spectral data. Essential oils abound in such minor constituents that might be of high importance for their (e.g. olfactory) properties. The presence of new minor constituents is usually inferred from gas chromatography mass spectrometry (GC-MS) analyses that provide only a mass spectrum and retention data, which are insufficient to allow a positive identification. OBJECTIVE: To identify a minor unknown constituent of the essential oil of Achillea abrotanoides (Vis.) Vis. (Asteraceae). METHODOLOGY: The application of chemical transformations (oxidation and reduction) performed directly on crude essential-oil samples, followed by preparative chromatography and detailed spectral analysis, to identify a new longipinane ketone from the mentioned sample. RESULTS: GC-MS analyses of the essential oil revealed, among other constituents, the presence of a known rare longipinane alcohol (α-longipinen-7ß-ol) representing 2.5% of the total GC-peak areas, and a related unidentified oxygenated sesquiterpene (3.8%). Interpretation of their mass spectra led to an assumption that the unidentified one could represent α-longipinen-7-one. Oxidation of the entire essential-oil sample by pyridinium chlorochromate confirmed the assumed relationship among the compounds and gave a simplified enriched mixture containing the ketone (ca. 16%). A straightforward chromatographic separation of the ketone was followed by corroboration of its structure by nuclear magnetic resonance (NMR) (one- and two-dimensional), infrared (IR) and MS. CONCLUSIONS: The complementing use of chemical transformations of crude essential oils, chromatographic separations, and detailed spectral analysis could have a more general application in the identification of new natural products.

Diethyl-Ether Flower Washings of Dianthus cruentus Griseb. (Caryophyllaceae): Derivatization Reactions Leading to the Identification of New Wax Constituents.

Some carnation species (Dianthus spp., Caryophyllaceae) exhibit a strong resistance to drought stress that is connected with the increased surface wax formation. Wax composition is unknown for the majority of Dianthus spp. Herein, mass spectral and gas chromatographic data, in combination with synthesis and chemical transformations (transesterification and synthesis of dimethyl disulfide adducts), enabled the identification of 151 constituents of diethyl-ether washings of fresh flowers of Dianthus cruentus Griseb. from Serbia. The flower wax contained, along with the dominant ubiquitous long-chain n-alkanes, homologous series of n- and branched (iso- and anteiso-) long-chain hexyl alkanoates/alkenoates and alkyl/alkenyl benzoates. The branching position in the mentioned hexyl esters was probed by synthesis of esters of three isomeric hexanols that were spectrally characterized (1 H- and 13 C-NMR, IR, MS). The washings also contained long-chain (Z)- and (E)-alkenes (C23 -C35 ) with several different double bond regiochemistries. Fifty-five of these constituents (eight hexyl esters, two benzoates, and forty-five alkenes) were detected for the first time in Plantae, while ten of these represent completely new compounds. The rare occurrence of these wax constituents makes them possible chemotaxonomic markers of this particular Dianthus sp.

Synthesis and Spectral Characterization of Asymmetric Azines Containing a Coumarin Moiety: The Discovery of New Antimicrobial and Antioxidant Agents.

Nine unsymmetrical azines containing a coumarin moiety were prepared by the reaction of the hydrazone of 4-hydroxy-3-acetylcoumarin with differently substituted aromatic aldehydes. The azines were fully spectrally characterized, including a complete assignment of 1 H- and 13 C-NMR resonances, and were assessed for their acute toxicities in the Artemia salina model. Their free radical scavenging activities were tested in the DPPH assay, and in vitro antimicrobial activities were determined against seven bacterial and two fungal strains. The azines containing a p-hydroxyphenyl group were shown to be the most effective antimicrobial agents, and in the case of resistant strains of Staphylococcus aureus and Acinetobacter baumannii, the activity was comparable to that of chloramphenicol. The derivative having a 3,5-dimethoxy-4-hydroxyphenyl group exhibited pronounced antioxidant power reacting rapidly and in 1 : 1 mol ratio with the DPPH radical.

Synthesis and antimicrobial activity of new 4-heteroarylamino coumarin derivatives containing nitrogen and sulfur as heteroatoms.

Synthesis, spectral analysis and bioactivity of new coumarin derivatives are described in this paper. Eight new coumarin derivatives were synthesized in moderate to good yields by condensation of 4-chloro-3-nitrocoumarin and the corresponding heteroarylamine. The synthesized compounds were tested for their in vitro antimicrobial activity, in a standard disk diffusion assay, against thirteen strains of bacteria and three fungal strains. They have shown a wide range of activity - from one completely inactive compound to medium active ones.