An isofagomine analogue with an amidine group in the 1,6-position.

The synthesis of an isofagomine analogue with an amidine group in the 1,6-position is described. Density functional theory calculations showed that this compound has a remarkably different charge distribution compared with isofagomine. This may explain why the amidine is a poor glycosidase inhibitor (IC > 50 µM against all tested enzymes) compared with isofagomine.

A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE).

The synthesis of four heterodimers in which the copper(I)-catalysed azide-alkyne cycloaddition was employed to connect a 1-deoxynojirimycin moiety with a benzotriazole scaffold is reported. The heterodimers were investigated as inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The heterodimers displayed preferential inhibition (> 9) of BuChE over AChE in the micromolar concentration range (IC = 7-50 µM).

Development of tacrine clusters as positively cooperative systems for the inhibition of acetylcholinesterase.

The synthesis of four tetra-tacrine clusters where the tacrine binding units are attached to a central scaffold linkers of variable lengths is described. The multivalent inhibition potencies for the tacrine clusters were investigated for the inhibition of acetylcholinesterase. Two of the tacrine clusters displayed a small but significant multivalent inhibition potency in which the binding affinity of each of the tacrine binding units increased up to 3.

COVID-19: molecular targets, drug repurposing and new avenues for drug discovery.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious infection that may break the healthcare system of several countries. Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. Finally, we also discuss patent protection issues, cost effectiveness and scalability of synthetic routes for some of the most studied repurposing candidates since these are key aspects to meet global demand for COVID-19 treatment.

Dealing with frequent hitters in drug discovery: a multidisciplinary view on the issue of filtering compounds on biological screenings.

: The timely identification biologically active chemicals, in disease relevant screening assays, is a major endeavor in drug discovery. The existence of frequent hitters (FHs) in non-related assays poses a formidable challenge in terms of whether to consider these molecules as chemical gold or promiscuous non-selective reactive trash (also known as PAINS - pan assay interference compounds).: In this review, the authors bring together expertize in synthetic chemistry, cheminformatics and biochemistry, three key areas for dealing with FHs.

Electrochemical and Morphological Investigations of Ga Addition to Pt Electrocatalyst Supported on Carbon.

This paper is consisted in the synthesis of platinum-based electrocatalysts supported on carbon (Vulcan XC-72) and investigation of the addition of gallium in their physicochemical and electrochemical properties toward ethanol oxidation reaction (EOR). PtGa/C electrocatalysts were prepared through thermal decomposition of polymeric precursor method at a temperature of 350°C. Six different compositions were homemade: PtGa/C, PtGa/C, PtGa/C, PtGa/C, PtGa/C, and Pt/C.