Licofelone-DPPC Interactions: Putting Membrane Lipids on the Radar of Drug Development

Autor(es)

Pereira-Leite, Catarina ^{[1, 2]} ; Lopes-de-Campos, Daniela ^[2] ; Fontaine, Philippe ^[3] ; Cuccovia, Iolanda M. ^[1] ; Nunes, Claudia ^[2] ; Reis, Salette ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, Av Prof Lineu Prestes 748, BR-05508000 Sao Paulo - Brazil

^[2] Univ Porto, Fac Farm, Dept Ciencias Quim, REQUIMTE, LAQV, Rua Jorge Viterbo Ferreira 228, P-4050313 Porto - Portugal

^[3] LOrme Merisiers, Synchrotron SOLEIL, BP48, F-91192 Gif Sur Yvette - France

• Tipo de documento: Artigo Científico
• Fonte: Molecules; v. 24, n. 3 FEB 1 2019.
• Citações Web of Science: 1

Resumo

(1) Background: Membrane lipids have been disregarded in drug development throughout the years. Recently, they gained attention in drug design as targets, but they are still disregarded in the latter stages. Thus, this study aims to highlight the relevance of considering membrane lipids in the preclinical phase of drug development. (2) Methods: The interactions of a drug candidate for clinical use (licofelone) with a membrane model system made of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were evaluated by combining Langmuir isotherms, Brewster angle microscopy (BAM), polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS), and grazing-incidence X-ray diffraction (GIXD) measurements. (3) Results: Licofelone caused the expansion of the DPPC isotherm without changing the lipid phase transition profile. Moreover, licofelone induced the reduction of DPPC packing density, while increasing the local order of the DPPC acyl chains. (4) Conclusions: The licofelone-induced alterations in the structural organization of phosphatidylcholine monolayers may be related to its pharmacological actions. Thus, the combination of studying drug-membrane interactions with the pharmacological characterization that occurs in the preclinical stage may gather additional information about the mechanisms of action and toxicity of drug candidates. Ultimately, the addition of this innovative step shall improve the success rate of drug development. (AU)

• Processo FAPESP: 13/08166-5 - Química em interfaces: interações de fármacos, peptídios e enzimas com membranas modelos
• Beneficiário: Iolanda Midea Cuccovia
• Modalidade de apoio: Auxílio à Pesquisa - Temático