Inibidores seletivos de prostaglandina endoperóxido sintase-2 (PGHS-2): nova estratégia para o tratamento da inflamação

Prostaglandins (PG's), produced from arachidonic acid metabolism, are potent mediators of inflammation. Nonsteroidal anti-inflammatory (NSAIDs) exert their effects by inhibition of prostaglandin endoperoxide synthase (PGHS) enzyme, which catalyses the first committed step in arachidonic acid metabolism. Two isoforms of PGHS are known: PGHS-1, constitutively expressed in most tissues, and is responsible for physiological production of PG's. The second isoform, PGHS-2, is induced by cytokines, mitogens and endotoxins in inflammatory cells, and appears to be responsible for the elevated production of PG's during inflammation. With the recent discovery of the inducible PGHS (PGHS-2), the medicinal chemist now possesses a novel target for designing therapeutic agents that could provide suitable anti-inflammatory activity without the ulcerogenic and renal side effects associated with currently available NSAIDs, all of which inhibit both PGHS-1 and PGHS-2.

Síntese e modificações de derivados heterocíclicos de D-arabinose: potenciais inibidores de glicose-6-fosfato isomerase e de glicosamina-6-fosfato sintase

The synthesis of -5-(D-arabino-1,2,3,4-tetrahydroxybutyl)tetrazole and -2-(D-arabino-1,2,3,4-tetra-acetoxybutyl)-5-methyl-1,3,4-oxadiazole from D-arabinose is described. Attempts at removing the protecting groups of the oxadiazole derivative were unsuccessful, leading to products resulting from the opening of the oxadiazole ring. The unprotected tetrazole derivative was selectively phosphorylated at the primary hydroxyl group with diethylphosphoryl chloride. The resulting 5-[D-arabino-4-(diethylphosphoryloxy)-1,2,3-trihydroxybutyl]tetrazole is a protected form of a potential inhibitor of the enzymes glucose-6-phosphate isomerase and glucosamine synthase.

A intrigante bioquímica da niacina: uma revisão crítica

Niacin (nicotinamide, nicotinic acid) interferes on homeostasis, DNA regulation, signaling and longevity. Nicotinic acid reduces synthesis of lipoproteins-apo-B and increases HDL. Its antilipemic action in liver produces: 1) inhibition of DGAT2, with decreased triacylglycerol synthesis, 2) downregulation of the b-chain of adenosine triphosphate synthase, leading to reduced HDL-apo-A-I catabolism. Nicotinic acid could increase redox potential in vascular endothelium. HM74A receptor activation in macrophages would be responsible for the release of prostaglandins, causing flushing in epidermis. HM74A agonists could assist in identifying antilipemic agents. Extended release niacin in combination with statin appears to protect cardiovascular system of patients with low HDL.