Coelobillardin,an iridoid glucoside dimer from Coelospermum billardieri

An isoflavanoid (6-->2) neoflavonoid dimer and a 4',5',7-trihydroxy-2'-methoxyisoflavone, both as the acetate derivatives were isolated from the heartwood of Dalbergia nitidula. Their structures were established by spectroscopic methods.     

Chemical composition and in-vitro antimicrobial activity of the essential oils of three Greek Achillea species

The chemical composition of the essential oils of Achillea holosericea, Achillea taygetea, Achillea fraasii was determined by GC/MS analysis. Among the ninety-five assayed constituents, camphor, borneol and 1,8-cineol were found to be the major components. The in-vitro antimicrobial activity of these essential oils was evaluated against six bacteria indicating that the first is totally inactive, while the other two possess moderate to strong activities mainly against the Gram negative strains. The essential oil of A. fraasii was also active against the tested pathogenic fungi.     

Megistolactone, a new alkaloid from Sarcomelicope megistophylla

A new quinolone alkaloid, megistolactone (1) was isolated from the bark of Sarcomelicope megistophylla. Its structure has been elucidated on the basis of MS and NMR data. From a biogenetic point of view, this compound should be considered as an oxidation product of 1,2,3,4-tetra-O-subsituted acridone alkaloids, which are also present in the bark.     

Design, synthesis and molecular simulation studies of dihydrostilbene derivatives as potent tyrosinase inhibitors

The synthesis, molecular modeling and biological evaluation of substituted deoxybenzoins and optimized dihydrostilbenes are reported. Preliminary structure-activity relationship data were elucidated and lead compounds suitable for further optimization were discovered. Dihydrostilbene 7 is a particularly potent inhibitor (IC(50)=8.44μM, more potent than kojic acid).     

The Bite of the Honeybee: 2-Heptanone Secreted from Honeybee Mandibles during a Bite Acts as a Local Anaesthetic in Insects and Mammals

Honeybees secrete 2-heptanone (2-H) from their mandibular glands when they bite. Researchers have identified several possible functions: 2-H could act as an alarm pheromone to recruit guards and soldiers, it could act as a chemical marker, or it could have some other function. The actual role of 2-H in honeybee behaviour remains unresolved. In this study, we show that 2-H acts as an anaesthetic in small arthropods, such as wax moth larva (WML) and Varroa mites, which are paralysed after a honeybee bite. We demonstrated that honeybee mandibles can penetrate the cuticle of WML, introducing less than one nanolitre of 2-H into the WML open circulatory system and causing instantaneous anaesthetization that lasts for a few minutes. The first indication that 2-H acts as a local anaesthetic was that its effect on larval response, inhibition and recovery is very similar to that of lidocaine. We compared the inhibitory effects of 2-H and lidocaine on voltage-gated sodium channels. Although both compounds blocked the hNav1.6 and hNav1.2 channels, lidocaine was slightly more effective, 2.82 times, on hNav.6. In contrast, when the two compounds were tested using an ex vivo preparation–the isolated rat sciatic nerve–the function of the two compounds was so similar that we were able to definitively classify 2-H as a local anaesthetic. Using the same method, we showed that 2-H has the fastest inhibitory effect of all alkyl-ketones tested, including the isomers 3- and 4-heptanone. This suggests that natural selection may have favoured 2-H over other, similar compounds because of the associated fitness advantages it confers. Our results reveal a previously unknown role of 2-H in honeybee defensive behaviour and due to its minor neurotoxicity show potential for developing a new local anaesthetic from a natural product, which could be used in human and veterinary medicine.     

Dorycnioside, a new phenylbutanone glucoside from Dorycnium pentaphyllum subsp. herbaceum

A new phenylbutanone glucoside, dorycnioside, was isolated from the methanol extract of the aerial parts of Dorycnium pentaphyllum subsp. herbaceum Vill. (Rouy) and identified as 4-(4'-O-beta-D-glucopyranosyl-3',5'-dimethoxyphenyl)-2-butanone (1). In addition, two known phenylbutanone glucosides, five flavonoids, one cyanogenic glucoside, one cyclitol and one hydroquinone glucoside were also isolated and identified. The major constituent of the methanol extract was found to be myricitrin. The structure of 1 was elucidated on the basis of its spectroscopic data. It is the first time that derivatives of phenylbutanone are isolated from the Leguminosae family.     

Synthesis and cytotoxic activity of a new potent daunomycinone derivative

The preparation and cytotoxic activity of 4′-azido-3′-bromo-3′-deamino-4′-deoxydaunorubicin is described. The new compound was found to be less active in vitro than adriamycin against L1210 and the sensitive cell lines KB-3-1 and MES-SA, but retained interesting cytotoxicity against the adriamycin resistant subline KB-A1 and the multidrug resistant MES-SA/Dx5 subline.     

Oleuropein, an Anti-oxidant Polyphenol Constituent of Olive Promotes α-Secretase Cleavage of the Amyloid Precursor Protein (AβPP)

Over the past decade, intense focus has been dedicated on investigating processes involved in the proteolysis of amyloid precursor protein (AβPP) and β-amyloid (Aβ) peptide metabolism, as possible targets for Alzheimer’s disease (AD) therapy. To this goal, considerable research has been targeted on potential therapeutic use of compounds promoting non-amyloidogenic processing of AβPP. One of these compounds, oleuropein, a polyphenol constituent of extra virgin olive oil exhibiting a wide range of pharmacological properties, was shown to interact non-covalently with Aβ, an interaction that might be related to a potential protective role of oleuropein against Aβ aggregation. In the present study, it was demonstrated that oleuropein treatment of HEK293 cells stably transfected with the isoform 695 of human AβPP (APP695) leads to markedly elevated levels of sAPPα and to significant reduction of Aβ oligomers. These effects were associated with increased activity of matrix metalloproteinase 9 (MMP-9), whereas no significant alterations in the expression of secretases TACE, ADAM-10 or BACE-1 were observed. Similar results were obtained using the human neuroblastoma cell line SK-N-SH. The experimental data reveal an anti-amyloidogenic effect of oleuropein and suggest a possible protective role for oleuropein against AD, extending the spectrum of beneficial properties of this naturally occurring polyphenol.     

Design, synthesis, and antiproliferative activity of some novel aminosubstituted xanthenones, able to overcome multidrug resistance toward MES-SA/Dx5 cells

A series of novel xanthenone aminoderivatives and their pyrazole-fused counterparts possessing structural analogy to the potent anticancer agent 9-methoxypyrazoloacridine (PZA) reported. These compounds exhibited an interesting cytotoxic activity against a panel of cell lines. Most noticeably, they retain activity against the multidrug resistant MES-SA/Dx5 subline, showing resistant factors close to 1.