Marie Kvasnicova

Over the last decades, soft corals have been proven a rich source of biologically active compounds, featuring a wide range of chemical structures. Herein, we investigated the chemistry of an alcyonarian of the genus Lemnalia (Neptheidae), specimens of which were collected from the coral reefs near Al Lith, on the south‐west coast of Saudi Arabia. A series of chromatographic separations led to the isolation of 31 sesquiterpenes, featuring mainly the nardosinane and neolemnane carbon skeletons, among which three ( 13 , 14 and 28 ) are new natural products. The metabolites isolated in sufficient amounts were evaluated in vitro in human tumor and non‐cancerous cell lines for a number of biological activities, including their cytotoxic, anti‐inflammatory, anti‐angiogenic, and neuroprotective activities, as well as for their effect on androgen receptor (AR)‐regulated transcription. Among the tested metabolites, compound 12 showed comparable neuroprotective activity to the positive control N ‐acetylcysteine, albeit at a 10‐fold lower concentration.

A library of 3‐aryl‐3‐azetidinyl acetic acid methyl ester derivatives was prepared from N ‐Boc‐3‐azetidinone employing the Horner‐Wadsworth‐Emmons reaction, rhodium(I)‐catalyzed conjugate addition of arylboronic acids, and subsequent elaborations to obtain N ‐unprotected hydrochlorides, N ‐alkylated and N ‐acylated azetidine derivatives. The compounds were evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, revealing several derivatives to possess AChE inhibition comparable to that of the AChE inhibitor rivastigmine. The binding mode of the AChE inhibitor donepezil and selected active compounds 26 and 27 within the active site of AChE was studied using molecular docking. Furthermore, the neuroprotective activity of the prepared compounds was evaluated in models associated with Parkinson's disease (salsolinol‐induced) and aspects of Alzheimer's disease (glutamate‐induced oxidative damage). Compound 28 showed the highest neuroprotective effect in both salsolinol‐ and glutamate‐induced neurodegeneration models, and its protective effect in the glutamate model was revealed to be driven by a reduction in oxidative stress and caspase‐3/7 activity.