Antileishmanial Activity and Cytotoxicity of ent-Beyerene Diterpenoids

We describe the in vitro and in vivo leishmanicidal activity of two diterpenes of the ent-beyerene type, as well as several derivatives. The results indicate that the 18-hydroxymethyl group is essential for the activity. Using in vitro assays, two compounds, 10 and 11, exhibited an EC50 of 1.1 and 1.3 g/mL, with SI 3.1 and 3.5 respectively, while cure was obtained in 50% of hamsters with natural diterpenoids 1 and 2, both topically applied as cream at 0.81 and 2.6% (w/w). Because of the low abundance of these diterpenoids in nature, one of them was prepared from stevioside. These results suggest that ent-beyerene diterpenoids 1 and 2 as potential candidates for cutaneous leishmaniasis chemotherapy by topical application. However, further studies should be conducted to optimize this biological activity, specially dose and therapeutic scheme.

• Autores: Murillo Mosquera, Jilmar Andrés; Gil Romero, Juan Fernando; Upegui Zapata, Yulieth Alexandra; Restrepo Agudelo, Adriana María; Robledo Restrepo, Sara María; Quiñones Fletcher, Winston; Echeverri López, Luis Fernando; Escobar Peláez, Gustavo; San Martin, Aurelio; Olivo, Horacio F.
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2019
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/47253
• Acceso en línea: https://hdl.handle.net/10495/47253
• Palabra clave: Línea Celular; Cell Line; Diterpenos; Diterpenes; Leishmania braziliensis; Leishmaniasis Cutánea; Leishmaniasis, Cutaneous; Macrófagos - efectos de los fármacos; Macrophages - drug effects; Mesocricetus; https://id.nlm.nih.gov/mesh/D008647; Tripanocidas; Trypanocidal Agents; https://id.nlm.nih.gov/mesh/D002460; https://id.nlm.nih.gov/mesh/D004224; https://id.nlm.nih.gov/mesh/D007892; https://id.nlm.nih.gov/mesh/D016773; https://id.nlm.nih.gov/mesh/D008264; https://id.nlm.nih.gov/mesh/D014344; ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
• Rights: openAccess
• License: http://creativecommons.org/licenses/by-nc-nd/4.0/