Anticholinesterase activity of endemic plant extracts from Soqotra

A total of 30 chloroform and methanol extracts from the following endemic Soqotran plants Acridocarpus socotranus Olive, Boswellia socotranao Balf.fil, Boswellia elongata Balf. fil., Caralluma socotrana N. Br, Cephalocroton socotranus Balf.f, Croton socotranus Balf. fil.., Dendrosicycos socotrana Balf.f., Dorstenia gigas Schweinf. ex Balf. fil., Eureiandra balfourii Cogn. & Balf. fil., Kalanchoe farinaceae Balf.f, Limonium sokotranum (Vierh) Radcl. Sm), Oldenlandia pulvinata, Pulicaria diversifolia( Balf. and Pulicaria stephanocarpa Balf. were screened for their acetylcholinesterase inhibitory activity by using in vitro Ellman method at 50 and 200 μg/ml concentrations. Chloroform extracts of Croton socotranus, Boswellia socotrana, Dorstenia gigas, and Pulicaria stephanocarpa as well as methanol extracts of Eureiandra balfourii exhibited inhibitory activities higher than 50 % at concentration of 200 μg. At a concentrations of 50 μg, the chloroform extract of Croton socotranus exhibited an inhibition of 40.6 %.Key words: plant extracts, acetylcholinesterase inhibitors, Soqotra, Alzheimer’s diseas

Bichromonol, a dimeric coumarin with anti-HIV activity from the stem bark of Hypericum roeperianum

Infectious diseases caused by viruses like HIV and SARS-COV-2 (COVID-19) pose serious public health threats. In search for new antiviral small molecules from chemically underexplored Hypericum species, a previously undescribed atropisomeric C8-C8’ linked dimeric coumarin named bichromonol (1) was isolated from the stem bark of Hypericum roeperianum. The structure was elucidated by MS data and NMR spectroscopy. The absolute configuration at the biaryl axis was determined by comparing the experimental ECD spectrum with those calculated for the respective atropisomers. Bichromonol was tested in cell-based assays for cytotoxicity against MT-4 (CC50 = 54 µM) cells and anti-HIV activity in infected MT-4 cells. It exhibits significant activity at EC50 = 6.6–12.0 µM against HIV-1 wild type and its clinically relevant mutant strains. Especially, against the resistant variants A17 and EFVR, bichromonol is more effective than the commercial drug nevirapine and might thus have potential to serve as a new anti-HIV lead

ANTICHOLINESTERASE ACTIVITY OF ENDEMIC PLANT EXTRACTS FROM SOQOTRA

A total of 30 chloroform and methanol extracts from the following endemic Soqotran plants Acridocarpus socotranus Olive, Boswellia socotranao Balf.fil, Boswellia elongata Balf. fil., Caralluma socotrana N. Br, Cephalocroton socotranus Balf.f, Croton socotranus Balf. fil.., Dendrosicycos socotrana Balf.f., Dorstenia gigas Schweinf. ex Balf. fil., Eureiandra balfourii Cogn. & Balf. fil., Kalanchoe farinaceae Balf.f, Limonium sokotranum (Vierh) Radcl. Sm), Oldenlandia pulvinata, Pulicaria diversifolia( Balf. and Pulicaria stephanocarpa Balf. were screened for their acetylcholinesterase inhibitory activity by using in vitro Ellman method at 50 and 200 µg/ml concentrations. Chloroform extracts of Croton socotranus, Boswellia socotrana, Dorstenia gigas, and Pulicaria stephanocarpa as well as methanol extracts of Eureiandra balfourii exhibited inhibitory activities higher than 50 % at concentration of 200 ï­g. At a concentrations of 50 ï­g, the chloroform extract of Croton socotranus exhibited an inhibition of 40.6 %

Influence of Pickling Process on Allium cepa and Citrus limon Metabolome as Determined via Mass Spectrometry-Based Metabolomics

Brine, the historically known food additive salt solution, has been widely used as a pickling media to preserve flavor or enhance food aroma, appearance, or other qualities. The influence of pickling, using brine, on the aroma compounds and the primary and secondary metabolite profile in onion bulb Allium cepa red cv. and lemon fruit Citrus limon was evaluated using multiplex metabolomics technologies. In lemon, pickling negatively affected its key odor compound “citral”, whereas monoterpene hydrocarbons limonene and γ-terpinene increased in the pickled product. Meanwhile, in onion sulphur rearrangement products appeared upon storage, i.e., 3,5-diethyl-1,2,4-trithiolane. Profiling of the polar secondary metabolites in lemon fruit via ultra-performance liquid chromatography coupled to MS annotated 37 metabolites including 18 flavonoids, nine coumarins, five limonoids, and two organic acids. With regard to pickling impact, notable and clear separation among specimens was observed with an orthogonal projections to least squares-discriminant analysis (OPLS-DA) score plot for the lemon fruit model showing an enrichment of limonoids and organic acids and that for fresh onion bulb showing an abundance of flavonols and saponins. In general, the pickling process appeared to negatively impact the abundance of secondary metabolites in both onion and lemon, suggesting a decrease in their food health benefits

Identification of a Bacteria-produced Benzisoxazole with Antibiotic Activity against Multi-drug Resistant Acinetobacter baumannii

The emergence of multi-drug resistant pathogenic bacteria represents a serious and growing threat to national healthcare systems. Most pressing is an immediate need for the development of novel antibacterial agents to treat Gram-negative multi-drug resistant infections, including the opportunistic, hospital-derived pathogen, Acinetobacter baumannii. Herein we report a naturally occurring 1,2-benzisoxazole with minimum inhibitory concentrations as low as 6.25 μg ml−1 against clinical strains of multi-drug resistant A. baumannii and investigate its possible mechanisms of action. This molecule represents a new chemotype for antibacterial agents against A. baumannii and is easily accessed in two steps via de novo synthesis. In vitro testing of structural analogs suggest that the natural compound may already be optimized for activity against this pathogen. Our results demonstrate that supplementation of 4-hydroxybenzoate in minimal media was able to reverse 1,2-benzisoxazole’s antibacterial effects in A. baumannii. A search of metabolic pathways involving 4-hydroxybenzoate coupled with molecular modeling studies implicates two enzymes, chorismate pyruvate-lyase and 4-hydroxybenzoate octaprenyltransferase, as promising leads for the target of 3,6-dihydroxy-1,2-benzisoxazole

Copper-catalyzed diastereo- and enantioselective desymmetrization of cyclopropenes: Synthesis of cyclopropylboronates

This document is the accepted manuscript version of a Published Work that appeared in final form in Journal of American Chemical Society 136.45, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see DOI: 10.1021/ja510419zA novel Cu-catalyzed diastereo- and enantioselective desymmetrization of cyclopropenes to afford nonracemic cyclopropylboronates is described. Trapping the cyclopropylcopper intermediate with electrophilic amines allows for the synthesis of cyclopropylaminoboronic esters and demonstrates the potential of the approach for the synthesis of functionalized cyclopropanesWe thank the European Research Council (ERC-337776) and MINECO (CTQ2012-35957) for financial support. M. T. and A. P. thank MICINN for RyC and JdC contract

UBIAD1 Mutation Alters a Mitochondrial Prenyltransferase to Cause Schnyder Corneal Dystrophy

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