| Author | Badoco, Fernanda Rafacho | |
| Author | Paula, Lucas A L | |
| Author | Orenha, Renato P | |
| Author | Mendes, Tiago M F | |
| Author | Squarisi, Iara S | |
| Author | El-Sakkary, Nelly | |
| Author | Loiola, Messias C | |
| Author | Katz, Naftale | |
| Author | Tavares, Denise C | |
| Author | Sairre, Mirela I | |
| Author | Parreira, Renato Luis T | |
| Author | Cabral, Fernanda Janku | |
| Author | Alegretti, Silmara M | |
| Author | Caffrey, Conor R | |
| Author | Magalhães, Lizandra G | |
| Access date | 2023-01-26T16:06:41Z | |
| Available date | 2023-01-26T16:06:41Z | |
| Document date | 2022 | |
| Citation | BADOCO, Fernanda Rafacho et al. EF24, a schistosomicidal curcumin analog: Insights from its synthesis and phenotypic, biochemical and cytotoxic activities. Chemico-Biological Interactions, v. 368, p. 110191, 2022. Doi: 10.1016/j.cbi.2022.110191 | en_US |
| ISSN | 0009-2797 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/56636 | |
| Language | eng | en_US |
| Publisher | Elsevier | en_US |
| Rights | restricted access | |
| Title | EF24, a schistosomicidal curcumin analog: Insights from its synthesis and phenotypic, biochemical and cytotoxic activities | en_US |
| Type | Article | |
| Abstract | 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. | en_US |
| Affilliation | Research Group on Natural Products. Center for Research in Sciences and Technology.University of Franca, Franca, SP, Brazil. | en_US |
| Affilliation | Research Group on Natural Products. Center for Research in Sciences and Technology.University of Franca, Franca, SP, Brazil. | en_US |
| Affilliation | Research Group on Natural Products. Center for Research in Sciences and Technology.University of Franca, Franca, SP, Brazil. | en_US |
| Affilliation | Department of Animal Biology. Institute of Biology. University of Campinas. Campinas, SP, Brazil. | en_US |
| Affilliation | Research Group on Natural Products. Center for Research in Sciences and Technology.University of Franca, Franca, SP, Brazil. | en_US |
| Affilliation | Center for Discovery and Innovation in Parasitic Diseases. Skaggs School of Pharmacy and Pharmaceutical Sciences. University of California San Diego. La Jolla, CA, USA. | en_US |
| Affilliation | Human and Natural Sciences Center. Federal University of ABC. Santo André, SP, Brazil. | en_US |
| Affilliation | Institute René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | Research Group on Natural Products. Center for Research in Sciences and Technology.University of Franca, Franca, SP, Brazil. | en_US |
| Affilliation | Human and Natural Sciences Center. Federal University of ABC. Santo André, SP, Brazil. | en_US |
| Affilliation | Research Group on Natural Products. Center for Research in Sciences and Technology.University of Franca, Franca, SP, Brazil. | en_US |
| Affilliation | Department of Animal Biology. Institute of Biology. University of Campinas. Campinas, SP, Brazil. | en_US |
| Affilliation | Department of Animal Biology. Institute of Biology. University of Campinas. Campinas, SP, Brazil. | en_US |
| Affilliation | Center for Discovery and Innovation in Parasitic Diseases. Skaggs School of Pharmacy and Pharmaceutical Sciences. University of California San Diego. La Jolla, CA, USA. | en_US |
| Affilliation | Research Group on Natural Products. Center for Research in Sciences and Technology. University of Franca. Franca, SP, Brazil. | en_US |
| Subject | Curcumin analog | en_US |
| Subject | EF24 | en_US |
| Subject | Schistosoma mansoni isolates | en_US |
| Subject | Schistosomicidal | en_US |
| Embargo date | 2099-12-31 | |
