Niko S. Radulović

Synthesis and antimicrobial activity of some new pyrazole derivatives containing a ferrocene unit.

A series of new imines and amines have been synthesized by condensation of 1H-3-ferrocenyl-1-phenylpyrazole-4-carboxaldehyde with the corresponding amines, followed by reduction with sodium borohydride. The synthesized compounds have been screened for their in vitro antimicrobial activity against 11 bacteria and three fungal/yeast strains, using disc diffusion and broth microdilution susceptibility assays. They have shown a wide range of activities, from completely inactive to the highly active compounds.

Synthesis, characterization, electrochemical studies and antitumor activity of some new chalcone analogues containing ferrocenyl pyrazole moiety

A series of new alpha,beta-unsaturated conjugated ketones containing ferrocenyl pyrazole unit were synthesized and fully characterized by IR and NMR spectroscopy. Electrochemical characterization of subject compounds was performed by means of cyclic voltametry. The in vitro cytotoxic activity of all the synthesized compounds was studied against cervix adenocarcinoma HeLa, melanoma Fem-x and myelogenous leukemia K562 cell lines by the MTT method. Derivative 1l containing 3-pyridyl moiety exhibited a better cytotoxic activity in the cell growth inhibition of K562 cell lines in comparison with cisplatin as a reference compound.

Toxic essential oils. Part II: Chemical, toxicological, pharmacological and microbiological profiles of Artemisia annua L. volatiles

Botanical drugs based on Artemisia annua L. (Asteraceae) are important in the treatment of malaria. Alongside with artemisinin, this aromatic species produces high and variable amounts of other chemicals that have mostly unknown biological/pharmacological activities. Herein, we have studied the toxicological/pharmacological profile of volatile constituents of a Serbian population of A. annua. Fifty-eight components were identified, among them, artemisia ketone (35.7%), α-pinene (16.5%) and 1,8-cineole (5.5%) were the most abundant ones. Significant variability of A. annua volatile profile was confirmed by means of agglomerative hierarchical cluster analysis indicating the existence of several different A. annua chemotypes. In an attempt to connect the chemical profile of A. annua oil with its biological/toxicological effects, we have evaluated in vivo and/or in vitro toxicity (including hepato- and nephrotoxicity/protection), antinociceptive, antioxidant (DPPH, ABTS and superoxide radical scavenging activity assays), enzyme inhibiting (protein kinase A and α-amylase) and antimicrobial potential of A. annua oil and of its constituents. Our results revealed that the beneficial properties of A. annua botanical drugs are not limited only to their antimalarial properties. Taking into account its relatively low toxicity, the usage of A. annua volatiles (at least of the herein studied population) does not represent a health risk.

Toxic essential oils: Anxiolytic, antinociceptive and antimicrobial properties of the yarrow Achillea umbellata Sibth. et Sm. (Asteraceae) volatiles

Many plant species are used for medicinal purposes without the knowledge of their possible toxic effect. The ethnopharmacologically renowned genus Achillea L. (Asteraceae) is even more troublesome in this respect since different taxa are believed to have the same beneficial properties as A. millefolium. According to the median lethal i.p. dose (LD(50)=853 mg/kg, mice), the volatiles of Achillea umbellata Sibth. et Sm. are more toxic than the thujone-containing essential oils (LD(50)>960 mg/kg). A GC-MS analysis of A. umbellata oil revealed the presence of a series of fragranyl esters (six new natural products). The major constituents of this oil, the rare monoterpene alcohol fragranol and fragranyl acetate, and one more ester (benzoate), as well as the oil itself, showed antianxiety, analgesic and, in some instances, paralyzing properties at 50-150 mg/kg but these are very likely sign of intoxication and not of possible beneficial effects of the plant volatiles. Testing of antimicrobial activity demonstrated that the oil possesses moderate activity against pathogenic microorganisms, but the effect of the oil differs in pro- and eukaryotic cells. According to the results obtained, fragranol may be considered as the main active principle responsible for the observed activity/toxicity.

Geranium macrorrhizum L. (Geraniaceae) Essential Oil: A Potent Agent Against Bacillus subtilis

The volatile hydrodistilled compounds from aerial parts and rhizomes of the ethnopharmacologically highly valued plant species Geranium macrorrhizum L. were screened for their antimicrobial activity in disc‐diffusion and microdilution assays. The assays pointed out to a very high and selective activity of the oils against Bacillus subtilis with minimum inhibitory concentrations (MIC) of 0.4–1.0 μg/ml. This prompted us to perform detailed compositional analyses of the oils. GC and GC/MS analyses allowed the identification of 283 constituents. The oils consisted mainly of sesquiterpenoids, the main ones being germacrone (49.7% in the oil from aerial parts) and δ‐guaiene (49.2% in rhizome oil). Significant qualitative and quantitative compositional differences in the oils from the two plant parts were observed. Further antimicrobial testing enabled us to determine that germacrone, the major constituent of the oil from aerial parts, was not the sole agent responsible for the observed activity.

Chemical composition and antioxidant and antimicrobial activities of essential oil of Allium sphaerocephalon L. subsp. sphaerocephalon (Liliaceae) inflorescences

BACKGROUND Allium sphaerocephalon is a wild-growing plant commonly used as an onion substitute. In this study the essential oil obtained from A. sphaerocephalon subsp. sphaerocephalon inflorescences was analysed by gas chromatography and gas chromatography/mass spectrometry and also evaluated for in vitro antioxidant and antimicrobial activities. The obtained results are reported for the first time and discussed with respect to the sulfur compounds detected in the essential oil. RESULTS Ninty-one compounds were identified, representing 91.6% (w/w) of the total oil. Major constituents of the analysed sample were shyobunol (15.3%), β-caryophyllene (8.1%), α-cadinol (7.8%), 3,5-diethyl-1,2,4-trithiolane (isomer II, 5.9%) and δ-cadinene (5.2%). The diluted oil had an antioxidant capacity of 160 000 ± 111 micromol α-tocopherol acetate equivalents g(-1). Its antimicrobial activity was evaluated against five bacterial and two fungal strains using the broth microdilution assay. Among the micro-organisms tested, the most susceptible strains were Pseudomonas aeruginosa (minimal inhibitory/bactericidal concentration = 0.08/2.5 mg mL(-1)) and Aspergillus niger (minimal inhibitory/fungicidal concentration = 0.31/0.63 mg mL(-1)). CONCLUSION The results showed that the examined species had strong antioxidant and antimicrobial properties and are in accordance with the popular use of plants belonging to the genus Allium in traditional medicine, emphasising the necessity of further detailed study of the active principles in Allium species.

Synthesis and Antimicrobial Activity of New 4-Heteroarylamino Coumarin Derivatives Containing Nitrogen and Sulfur as Heteroatoms

ynthesis, 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.

Comparative study of the leaf volatiles of Arctostaphylos uva-ursi (L.) Spreng. and Vaccinium vitis-idaea L. (Ericaceae).

The first GC and GC/MS analyses of the essential oils hydrodistilled from dry leaves of Arctostaphylos uva-ursi and Vaccinium vitis-idaea enabled the identification of 338 components in total (90.4 and 91.7% of the total GC peak areas, respectively). Terpenoids, fatty acids, fatty acid- and carotenoid derived compounds were predominant in the two samples. Both oils were characterized by high relative percentages of α-terpineol and linalool (4.7-17.0%). Compositional data on the volatiles of the presently analyzed and some other Ericaceae taxa (literature data) were mutually compared by means of multivariate statistical analyses (agglomerative hierarchical cluster analysis and principal component analysis). This was done in order to determine, based on the essential oil profiles, possible mutual relationships of the taxa within the family, especially that of species from the genera Arctostaphylos and Vaccinium. Results of the chemical and statistical analyses pointed to a strong relation between the genera Vaccinium and Arctostaphylos.

Toxic essential oils. Part III: Identification and biological activity of new allylmethoxyphenyl esters from a Chamomile species (Anthemis segetalis Ten.)

To determine the exact structure of previously tentatively identified minor essential-oil constituents of a Chamomile species (Antemis segetalis Ten. (Asteraceae)), we have synthesized a small combinatorial library of 54 regioisomeric allylmethoxyphenyl pentanoates and 2-pentenoates (49 completely new compounds). GC-MS in combination with 1D- and 2D-NMR analyses of the library compounds provided unambiguous data that led to a straightforward identification of the mentioned A. segetalis constituents as eugenyl angelate, 2-methylbutanoate and 3-methylbutanoate (0.21, 0.22, and 0.13 mg/100 g of fresh plant material, respectively). To assess the safety and potential beneficial pharmacological uses of these naturally occurring esters and several other library compounds (these were tested to provide relevant data for a SAR (structure-activity relationship) analysis), we have studied the effect of these compounds in several models of toxicity (acute toxicity against Artemia salina, cytotoxicity against two cell lines (fibroblast and melanoma)), as well as their acetylcholinesterase inhibitory and antibacterial activities. Anthemis segetalis constituents showed low to moderate activity in all tests. The obtained results suggest that the intake of these compounds in naturally available amounts, on their own, would probably not represent a risk to human health but the possible adverse interactions with the plant matrix should not be neglected.

Antimicrobial Activity of Nepeta rtanjensis Essential Oil

Abstract The antimicrobial activity and the composition of the essential oil of aerial parts of Nepeta rtanjensis Diklić et Milojević wild growing and cultivated in Serbia were evaluated. The main compound in both samples was characterized as 4aα,7α,7aβ-nepetalactone with 83.6% (wild) and 77.9% (cultivated). α-Copaene, germacrene D and δ-cadinene were present less than 5% in the oils. The antimicrobial activity of the oils was investigated by disk diffusion method. The oil-ethanol solution in three dilutions, tested against fve bacteria and a fungus, was effective towards all bacteria but not against Aspergillus niger. The oils showed bacteriostatic activity even in 1:60 dilution.