Pumilacidins from the Octocoral-Associated Bacillus sp. DT001 Display Anti-Proliferative Effects in Plasmodium falciparum
Daniel Torres-Mendoza,
Lorena M. Coronado,
Laura M. Pineda,
Héctor M. Guzmán,
Pieter C. Dorrestein,
Carmenza Spadafora,
Marcelino Gutiérrez
Affiliations
Daniel Torres-Mendoza
Centro de Biodiversidad y Descubrimiento de Drogas, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Panama, Apartado 0843-01103, Panama
Lorena M. Coronado
Centro de Biología Celular y Molecular de Enfermedades, INDICASAT AIP, Panama, Apartado 0843-01103, Panama
Laura M. Pineda
Centro de Biología Celular y Molecular de Enfermedades, INDICASAT AIP, Panama, Apartado 0843-01103, Panama
Héctor M. Guzmán
Smithsonian Tropical Research Institute, Balboa, Ancon P.O. Box 0843-03092, Panama
Pieter C. Dorrestein
Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093, USA
Carmenza Spadafora
Centro de Biología Celular y Molecular de Enfermedades, INDICASAT AIP, Panama, Apartado 0843-01103, Panama
Marcelino Gutiérrez
Centro de Biodiversidad y Descubrimiento de Drogas, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Panama, Apartado 0843-01103, Panama
Chemical examination of the octocoral-associated Bacillus species (sp.) DT001 led to the isolation of pumilacidins A (1) and C (2). We investigated the effect of these compounds on the viability of Plasmodium falciparum and the mechanism of pumilacidin-induced death. The use of inhibitors of protein kinase C (PKC) and phosphoinositide 3-kinase (PI3K) was able to prevent the effects of pumilacidins A and C. The results indicated also that pumilacidins inhibit parasite growth via mitochondrial dysfunction and decreased cytosolic Ca2+.
