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EF24, a schistosomicidal curcumin analog: Insights from its synthesis and phenotypic, biochemical and cytotoxic activities.
Badoco, Fernanda R; Paula, Lucas A L; Orenha, Renato P; Mendes, Tiago M F; Squarisi, Iara S; El-Sakkary, Nelly; Loiola, Messias C; Katz, Naftale; Tavares, Denise C; Sairre, Mirela I; Parreira, Renato Luis T; Janku Cabral, Fernanda; Alegretti, Silmara M; Caffrey, Conor R; Magalhães, Lizandra G.
Afiliación
  • Badoco FR; Research Group on Natural Products, Center for Research in Sciences and Technology, University of Franca, Franca, SP, Brazil.
  • Paula LAL; Research Group on Natural Products, Center for Research in Sciences and Technology, University of Franca, Franca, SP, Brazil.
  • Orenha RP; Research Group on Natural Products, Center for Research in Sciences and Technology, University of Franca, Franca, SP, Brazil.
  • Mendes TMF; Department of Animal Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
  • Squarisi IS; Research Group on Natural Products, Center for Research in Sciences and Technology, University of Franca, Franca, SP, Brazil.
  • El-Sakkary N; Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
  • Loiola MC; Human and Natural Sciences Center, Federal University of ABC, Santo André, SP, Brazil.
  • Katz N; Research Center René Rachou, Oswaldo Cruz Foundation, Belo Horizonte, Minas Gerais, Brazil.
  • Tavares DC; Research Group on Natural Products, Center for Research in Sciences and Technology, University of Franca, Franca, SP, Brazil.
  • Sairre MI; Human and Natural Sciences Center, Federal University of ABC, Santo André, SP, Brazil.
  • Parreira RLT; Research Group on Natural Products, Center for Research in Sciences and Technology, University of Franca, Franca, SP, Brazil.
  • Janku Cabral F; Department of Animal Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
  • Alegretti SM; Department of Animal Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
  • Caffrey CR; Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA. Electronic address: ccaffrey@health.ucsd.edu.
  • Magalhães LG; Research Group on Natural Products, Center for Research in Sciences and Technology, University of Franca, Franca, SP, Brazil. Electronic address: lizandra.magalhaes@unifran.edu.br.
Chem Biol Interact ; 368: 110191, 2022 Dec 01.
Article en En | MEDLINE | ID: mdl-36181831
Praziquantel (PZQ) is the only drug available for community-based control programs which aim to reduce the prevalence and morbidity associated with schistosomiasis. Here, we synthesized and evaluated the schistosomicidal, biochemical and cytotoxic activities of EF24, a synthetic curcumin analog, against different isolates of Schistosoma mansoni. EF24 elicited marked phenotypic alterations at 10 µM against schistosomula and 42-day-old adult worms of the Naval Medical Research Institute (NMRI) isolate. EF24 had 50% effective concentration (EC50) values of <10 µM against the Luis Evangelista (LE), Sergipe (SE), Belo Horizonte (BH) and Belo Horizonte less sensitive to PZQ (BH < PZQ) isolates of adult S. mansoni; however, the respective sensitivities of these isolates differed. Changes in the parasite included, vacuolization of the tegument and focal lysis of the interstitial tissue and muscle layers. Against 28-day-old juvenile worms (LE isolate), EF24 was about three times more potent than PZQ. After 6 h at 12.5 µM, EF24 increased reactive oxygen species (ROS) and the activity of the antioxidant enzyme, glutathione-S-transferase (GST), by 32 and 19% in female and male adult worms, respectively. By contrast, after 6 h at 12.5 µM glutathione reductase (GR) activity decreased by 43 and 30%, and glutathione peroxidase (GPx) activity decreased by 67 and 44% in females and males, respectively. EF24 was less cytotoxic to mammalian host cells than to S. mansoni, with selectivity indexes (SIs) of 1.8-3.4 and 2.7-7.5 for juvenile and adult worms, respectively. Given the current evidence for the in vitro schistosomicidal effect of EF24, the structure-activity relationship of additional analogs to identify new candidates for schistosomiasis treatment is warranted.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Schistosoma mansoni / Esquistosomicidas / Curcumina Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Chem Biol Interact Año: 2022 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Irlanda
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Schistosoma mansoni / Esquistosomicidas / Curcumina Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Chem Biol Interact Año: 2022 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Irlanda