Uncovering the Potential of Lipid Drugs: A Focus on Transient Membrane Microdomain-targeted Lipid Therapeutics

Autor(es)

Schneider Alves, Anna Carolina ; Cardoso, Raquel Soares ; de Oliveira Neto, Xisto Antonio ; Kawano, Daniel Fabio

• Tipo de documento: Artigo Científico
• Fonte: MINI-REVIEWS IN MEDICINAL CHEMISTRY; v. 22, n. 18, p. 14-pg., 2022-01-01.

Resumo

Membrane lipids are generally viewed as inert physical barriers, but many vital cellular processes greatly rely on the interaction with these structures, as expressed by the membrane hypothesis that explain the genesis of schizophrenia, Alzheimer's and autoimmune diseases, chronic fatigue or cancer. The concept that the cell membrane displays transient membrane microdomains with distinct lipid composition providing the basis for the development of selective lipid-targeted therapies, the membrane-lipid therapies (MLTs). In this concern, medicinal chemists may design therapeutically valuable compounds 1) with a higher affinity for the lipids in these microdomains to restore the normal physiological conditions, 2) that can directly or 3) indirectly (via enzyme inhibition/activation) replace damaged lipids or restore the regular lipid levels in the whole membrane or microdomain, 4) that alter the expression of genes related to lipid genesis/metabolism or 5) that modulate the pathways related to the membrane binding affinity of lipid-anchored proteins. In this context, this mini-review aims to explore the structural diversity and clinical applications of some of the main membrane and microdomain-targeted lipid drugs. (AU)

• Processo FAPESP: 18/08585-1 - Planejamento e síntese de novos fosfolipídios capazes de induzir seletivamente a apoptose de células tumorais pela atuação em "lipid rafts"
• Beneficiário: Daniel Fábio Kawano
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/22817-2 - Síntese de novos fosfolipídios antitumorais inibidores da enzima trifosfato de citidina (CTP): fosfocolina citidililtransferase humana
• Beneficiário: Xisto Antonio de Oliveira Neto
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 22/01239-6 - Síntese de inibidores de ceramidases ácidas como possíveis ferramentas no tratamento oral do câncer de próstata
• Beneficiário: Xisto Antonio de Oliveira Neto
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/05876-2 - Planejamento e síntese de novos fosfolipídios capazes de induzir seletivamente a apoptose de células tumorais pela atuação em lipid rafts
• Beneficiário: Anna Carolina Schneider Alves
• Modalidade de apoio: Bolsas no Brasil - Doutorado