The combination of peptides and antibiotics may be key to eliminating the parasites that cause leishmaniasis and avoiding the toxicity to humans and animals caused by current drugs.
Coordinated by researchers at the Autonomous University of Barcelona, this study opens the door to new and more effective treatments for the disease.
Leishmaniasis is caused by the protozoan leishmania parasite, which is transmitted by the bite of an infected sandfly. In rich countries, the disease primarily affects dogs, but in other countries it can be devastating to human health and can be fatal, from ulcers to bone marrow, liver and spleen damage. There is.
The WHO currently estimates that more than 1 billion people live in areas where Reichmania disease is endemic and that there are more than 1 million new cases each year.
Therefore, there is an urgent need to find new, efficient and selective alternatives to leishmaniasis chemotherapy that can reduce the harmful side effects of existing drugs such as paromomycin and miltefosine.
UAB Chemistry Lecturers Rosa Maria Ortuño and Ona Illa coordinated interdisciplinary studies to find new anti-leishmaniatic therapies.
A group of Lecturer Jean-Didier Maréchal from the same department, Carme Nogués from UAB Cell Biology, Physiology and Immunology, and Luis Rivas, a researcher at CIB Margarita Salas, also participated in the study. IQAC CSIC (Madrid) and Miriam Royo-CSIC (Barcelona).
This study is the preparation and biological evaluation of a new cell-penetrating peptide (CPP) that, through antibiotic binding, acts as a vehicle or vector for drugs, allowing it to enter the parasite’s cell membrane and be released internally. Consists of. That death.
As a result, it is more effective and requires fewer oral doses at the same time. In addition, synthetic CPP is not toxic to mammalian cells, but toxic to leishmaniasis.
The idea of using CPP to treat leishmaniasis is unclear, but the importance of this study is its high cell permeability and the selectivity of newly synthesized and studied peptides (mammalian and parasite cells). It is in... “
Rosa Maria Ortuño, Lecturer, Department of Chemistry, Autonomous University of Barcelona
In particular, this study has helped to study peptides composed of covalent bonds and non-protein amino acids of doxorubicin (Dox), a drug that is also used to treat cancer.
Free Dox is inactive when incubated with Leishmania because it cannot penetrate inside, but Dox-PPC conjugates have been shown to be toxic at very low concentrations (above 1 mM). Its cell penetration capacity has been rationalized through molecular modeling research.
The results are very promising, “we still need a lot of research before we can think of new drugs, but we are now a bit closer to our goal,” Ortuño concludes.
Barcelona Autonomous University
Illa, O. , et al.. (2020) Chiral cyclobutane-containing cell-permeable peptide as a selective vector for anti-leishmania drug delivery systems. International Journal of Molecular Science.. doi.org/10.3390/ijms21207502.