47 research outputs found
Chiral bistacrine analogues : synthesis, cholinesterase inhibitory activity and a molecular modeling approach
Cholinesterase enzymes are important targets for the therapy of Alzheimer’s disease. Tacrine-based dual binding site cholinesterases inhibitors are potential disease-modifying anti-Alzheimer drug candidates. In the present work, we described the synthesis of a series of chiral homo- and heterodimers of bis(7)-tacrine connected by a heptylene chain as a spacer with the methyl substituent at the C-3 position of the alicyclic region of tacrine nucleus and/or a chlorine atom attached to the C-6. Friedländer cyclocondensation between (R) or (S) 3-methylcyclohexanone prepared from monoterpene pulegone and o-aminobenzoic acids in the presence of POCl3 afford 9-chloroacridines as intermediates, which were used to the synthesis of homo- and heterodimers. All compounds demonstrated to be potent inhibitors of acetylcholinesterase (AChE) at low nanomolar concentration and showed selectivity for AChE over butyrylcholinesterase (BuChE). Furthermore, the affinity difference between enantiomeric bis(7)-tacrine analogues series indicated some degree of stereoselectivity in the active site of AChE for chiral bis-cognitin compounds
Processo multicomponente para sÃntese de compostos hÃbridos contendo os núcleos tetraidroacridina e imidazol 1,2,4,5-tetrassubstituÃdos para fins farmacológicos e produtos
Universidade Federal do Rio Grande do SulCiências Básicas da SaúdeQuÃmicaFarmáciaDepositad
Imprinted antibody responses against SARS-CoV-2 Omicron sublineages
SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters result in potent plasma neutralizing activity against Omicron BA.1 and BA.2 and that breakthrough infections, but not vaccination-only, induce neutralizing activity in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1 and BA.2 receptor-binding domains whereas Omicron primary infections elicit B cells of narrow specificity. While most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant antibody, that is unaffected by any Omicron lineage spike mutations and is a strong candidate for clinical development
Imprinted antibody responses against SARS-CoV-2 Omicron sublineages
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters elicit plasma-neutralizing antibodies against Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5, and that breakthrough infections, but not vaccination alone, induce neutralizing antibodies in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1, BA.2, and BA.4/5 receptor-binding domains, whereas Omicron primary infections elicit B cells of narrow specificity up to 6 months after infection. Although most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant–neutralizing antibody that is a strong candidate for clinical development
Indium mediated isoprenylation of carbonyl compounds with 2-bromomethyl-1,3-butadiene: a short synthesis of (+-)ipsenol
A isoprenilação de aldeÃdos e cetonas foi realizada através da inserção seletiva de Ãndio sobre uma mistura de 2-bromometil-1,3-butadieno e seus isômeros vinÃlicos, com bons rendimentos. Uma sÃntese rápida do (±)-ipsenol, feromônio de agregação do besouro Ips paraconfusus, demonstra a utilidade deste método em sÃntese orgânica.Isoprenylation of aldehydes and ketones was directly performed by selective indium insertion on a mixture of 2-bromomethyl-1,3-butadiene and its vinylic isomers in good yields. A short synthesis of (±)-ipsenol, an aggregation pheromone of the Ips paraconfusus bark beetle, demonstrates the utility of this method in organic synthesis
El Eco de Santiago : diario independiente: Año XXI Número 7104 - 1916 Enero 22
Numeración errónea en el original
Indium mediated isoprenylation of carbonyl compounds with 2-bromomethyl-1,3-butadiene: a short synthesis of (+-)ipsenol
A isoprenilação de aldeÃdos e cetonas foi realizada através da inserção seletiva de Ãndio sobre uma mistura de 2-bromometil-1,3-butadieno e seus isômeros vinÃlicos, com bons rendimentos. Uma sÃntese rápida do (±)-ipsenol, feromônio de agregação do besouro Ips paraconfusus, demonstra a utilidade deste método em sÃntese orgânica.Isoprenylation of aldehydes and ketones was directly performed by selective indium insertion on a mixture of 2-bromomethyl-1,3-butadiene and its vinylic isomers in good yields. A short synthesis of (±)-ipsenol, an aggregation pheromone of the Ips paraconfusus bark beetle, demonstrates the utility of this method in organic synthesis