title: Antileishmanial activity of warifteine: a bisbenzylisoquinoline alkaloid isolated from Cissampelos sympodialis Eichl. (Menispermaceae).
abstract: Leishmania (L.) chagasi is the etiological agent of visceral leishmaniasis, an important endemic zoonosis in the American continent, as well as in many other countries in Asia, Africa, and Mediterranean Europe. The treatment is difficult due to the high toxicity of the available drugs, high costs, and emergence of resistance in the parasites. Therefore, there is an urgent need for new leishmanicidal agents. The bisbenzylisoquinoline alkaloids have been related to antibacterial, antiprotozoal, and antifungal activities. The aim of this study was to evaluate the growth inhibitory activity of warifteine (bisbenzylisoquinoline alkaloid) against L. chagasi promastigotes in axenic cultures and the occurrence of drug-induced ultrastructural changes in the parasite. This bisbenzylisoquinoline alkaloid was isolated from the leaves and roots of Cissampelos sympodialis Eichl. (Menispermaceae), a plant commonly used for the treatment of various diseases in Brazilian folk medicine. Using the purified warifteine, the 50% inhibitory concentration (IC₅₀) was determined at 0.08 mg/mL after 72 h in culture, inducing significant changes in the parasite morphology, like aberrant multisepted forms and blebs in the plasma membrane. In conclusion, warifteine represents an attractive candidate for future pharmacological studies aiming new leishmanicidal drugs.
authors.affiliation: Departamento de Histologia e Embriologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Avenida Professor Moraes Rego 1265, Cidade Universitária, 50670-901 Recife, PE, Brazil. ecs@ufpe.br
authors.forename: Eliete
authors.initials: E
authors.lastname: Cavalcanti da Silva
authors.forename: Cynthia
authors.initials: C
authors.lastname: Dias Rayol
authors.forename: Paloma Lys
authors.initials: PL
authors.lastname: Medeiros
authors.forename: Regina Célia Bressan Queiroz
authors.initials: RC
authors.lastname: Figueiredo
authors.forename: Márcia Regina
authors.initials: MR
authors.lastname: Piuvezan
authors.forename: José Maria
authors.initials: JM
authors.lastname: Brabosa-Filho
authors.forename: Alexsandro
authors.initials: A
authors.lastname: Fernandes Marinho
authors.forename: Teresinha Gonçalves
authors.initials: TG
authors.lastname: Silva
authors.forename: Gardenia Carmen Gadelha
authors.initials: GC
authors.lastname: Militão
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Pimentel Cassilhas
authors.forename: Paulo
authors.initials: P
authors.lastname: Paes de Andrade
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D061245:Axenic Culture; D044182:Benzylisoquinolines / Q000302:isolation & purification* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D031606:Cissampelos / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects* / Q000648:ultrastructure; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D018515:Plant Leaves / Q000737:chemistry; D013997:Time Factors
chemical_list: D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D000981:Antiprotozoal Agents; D044182:Benzylisoquinolines; C003931:warifteine