Lupresan, a new drug that prevents or reverts the formation of nonbilayer phospholipid arrangements that trigger a murine lupus resembling human lupus

Albany Reséndiz-Mora, Carla Landa, Sandra Sánchez-Barbosa, Sergio Meza-Toledo, Juan Carlos Santiago-Hernández, Carlos Wong, Isabel Baeza, Carlos Wong-Baeza

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Non-bilayer phospholipid arrangements (NPA) are lipid associations different from the bilayer, formed by the interactions of conic anionic lipids and divalent cations that produce an inverted micelle which is inserted between the lipid layers, so the polar heads of the outer lipids spread and expose new antigens. Since these structures are transient, they are not immunogenic, but if they are stabilized by drugs, such as chlorpromazine, they become immunogenic and induce anti-NPA antibodies that trigger a lupus-like disease in mice. Chloroquine is a drug used for the treatment of lupus; chloroquine has a quinoline ring and two positive charges that interact with conic anionic lipids and prevent or revert the formation of NPA. However, the polyamine spermidine is more effective, since it has three positive charges and interacts with more lipids, but polyamines cannot be used as drugs, because they are highly toxic. Here we report the design and synthesis of Lupresan, an analogous of chloroquine with its quinoline ring but with three positive charges. Lupresan is more effective in preventing or reverting the formation of NPA than chloroquine or spermidine, and as a consequence, it decreased auto-antibody titers and healed the malar rash in mice with lupus to a greater extent than chloroquine. A drug as Lupresan could be used for the treatment of human lupus.

Original languageEnglish
Pages (from-to)275-280
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume509
Issue number1
DOIs
StatePublished - 29 Jan 2019

Keywords

  • Cell membrane
  • Chloroquine
  • Non-bilayer phospholipid arrangements
  • Systemic lupus erythematosus treatment

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