Lupus mice treated with Lupresan decreased auto-antibodies titers and improve facial lesions

Abstract

Abstract The nonbilayer phospholipid arrangements (NPA) are lipid associations different from the bilayer that are transient, so they are not immunogenic. But if they are stabilized by some drugs such as chlorpromazine, they become immunogenic and induce anti-NPA antibodies, which are found in patients with Lupus and are the ones that trigger a disease similar to Lupus in mice. Chloroquine, a drug used in the treatment of malaria, has been widely used to treat patients with Lupus; however, the mechanism of action by which it works in the treatment of Lupus is not known with certainty. In our research group, we have shown that chloroquine prevents the formation of NPA or reverts the formed, so it could be its mechanism in the treatment of Lupus. On the other hand, we have also shown that the polyamine spermidine is more effective than chloroquine in preventing the formation of NPA or in reverting the formed ones. Probably because this polyamine better stabilizes the lipid bilayer, because it has 3 positive charges in its structure at physiological pH, unlike the chloroquine that only has two. However, although polyamines participate in many biological functions, they cannot be used as drugs because when they have been administered in humans, they produce hematuria, proteinuria, renal failure and nephrotoxicity. In addition, in laboratory animals, they produce seizures, coma and death. So, in this work we design and synthesize Lupresan, an analogue of chloroquine with three positive charges at physiological pH. Lupresan was more effective in reverting or preventing the formation of NPA than chloroquine or spermidine, and as a result, it decreased auto-antibodies titers and healed the malar rash in mice with lupus to a greater extent than chloroquine.