Methods: A set of innovative algorithms is used for the fast calculation and interpretation of electron-density attributes of molecular structures at the quantum level for rapid discovery of prospective pharmaceuticals. Potency and efficacy, as well as additional physicochemical, metabolic, pharmacokinetic, safety, permeability and other properties were characterized by the procedure. Once quantum models are developed and experimentally validated, the methodology provides a straightforward implementation for lead discovery, compound optimizzation and de novo molecular

design.

Results: Starting with a diverse training set of 26 well-known anti-malarial agents combined with 1730 moderately active and inactive molecules, novel compounds that have strong anti-malarial activity, low cytotoxicity and structural dissimilarity from the training set were

discovered and experimentally validated. Twelve compounds were identified selleck compound in silico and tested in vitro; eight of them showed anti-malarial activity (IC50 <= 10 mu M), with six being very effective (IC50 <= 1 mu M), and four exhibiting low nanomolar potency. The most active compounds were also tested for mammalian cytotoxicity and found to be non-toxic, with a FRAX597 manufacturer therapeutic index of more than 6,900 for the most active compound.

Conclusions: Gradient’s metric modelling approach and electron-density molecular representations can be powerful tools in the discovery and design of novel anti-malarial compounds. Since the quantum models are agnostic of the particular biological target, the technology can account for different mechanisms of action and be used for de novo design of small molecules with activity against not only the asexual phase of the malaria parasite, but also against the liver stage of the parasite development, which may lead to true causal prophylaxis.”
“Enterovirus 71 (EV71) causes life-threatening disease outbreaks

in young children in Asia. This cohort study was conducted to understand the dynamics of maternal EV71 antibodies in Taiwanese young infants. Approximately 50% of neonates had detectable EV71 neutralizing antibodies, which SB431542 molecular weight declined to almost undetectable levels by 6 months of age.”
“A novel series of polycyclic amines, containing nitrogen monoxide donating moieties, were synthesised and tested for calcium channel and N-methyl-D-aspartate receptor modulating activity. The synthesised compounds were classified into two groups, based on their nitrogen monoxide donating moieties: unsaturated nitro compounds (1, 2 and 3) and nitro esters, or nitrates (4, 5 and 6). The nitrates were obtained via the reaction of hydroxyl functionalities with thionylchloride nitrate. All of the compounds synthesised exhibited significant (p < 0.01) S-nitrosylation capacity. The calcium channel activity of the polycyclic amines was evaluated using a KCl mediated fluorescent calcium flux assay.