The Bioactivity of Xylene, Pyridine, and Pyrazole Aza Macrocycles against Three Representative <i>Leishmania</i> Species

• Main Authors: Álvaro Martín-Montes (Author), Álvaro Martínez-Camarena (Author), Alberto Lopera (Author), Irene Bonastre-Sabater (Author), M. Paz Clares (Author), Begoña Verdejo (Author), Enrique García-España (Author), Clotilde Marín (Author)
• Format: Book
• Published: MDPI AG, 2023-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/pharmaceutics15030992; 1999-4923
• Keywords: <i>Leishmania</i>; chemotherapy; pyridine; pyrazole; macrocycles; mechanism of action; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 15, Iss 3, p 992 (2023)

Due to the urgent need for finding effective and free of secondary effect treatments for every clinical form of Leishmaniasis, a series of synthetic xylene, pyridine and, pyrazole azamacrocycles were tested against three <i>Leishmania</i> species. A total of 14 compounds were tested against J774.2 macrophage cells which were models for host cells, and against promastigote and amastigote forms of each studied <i>Leishmania</i> parasite. Amongst these polyamines, one proved effective against <i>L. donovani,</i> another one for <i>L. braziliensis</i> and <i>L. infantum,</i> and another one was selective solely for <i>L. infantum.</i> These compounds showed leishmanicidal activity and reduced parasite infectivity and dividing ability. Action mechanism studies gave a hint that compounds were active against <i>Leishmania</i> due to their ability to alter parasite metabolic pathways and reduce (except Py33333) parasitic Fe-SOD activity.