| Full text | |
| Author(s): Show less - |
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.
;
Cabral, Fernanda Janku
;
Alegretti, Silmara M.
;
Caffrey, Conor R.
;
Magalha, Lizandra G.
Total Authors: 15
|
| Document type: | Journal article |
| Source: | Chemico-Biological Interactions; v. 368, p. 11-pg., 2022-10-13. |
| 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 schistoso-micidal, biochemical and cytotoxic activities of EF24, a synthetic curcumin analog, against different isolates of Schistosoma mansoni. EF24 elicited marked phenotypic alterations at 10 mu M 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 mu M 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 mu M, 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, respec-tively. By contrast, after 6 h at 12.5 mu M 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. (AU) | |
| FAPESP's process: | 17/24856-2 - The Mechanism of the Substitution Reaction of the Ligand Nitrosyl by Aqua in Ruthenium Coordination Compounds |
| Grantee: | Renato Pereira Orenha |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 18/50011-2 - Exploring turmeric curcuminoids to treat schistosomiasis: an evaluation of their pre-clinical potential |
| Grantee: | Lizandra Guidi Magalhães |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 15/01394-8 - Study of EF-24 curcumin analogue and praziquantel in biochemical and morphological aspects involved in the cell death of the Schistosoma mansoni parasite |
| Grantee: | Fernanda Rafacho Badoco |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 14/02018-7 - Evaluation of curcumin analog EF24 in Schistosoma mansoni adult worms" |
| Grantee: | Fernanda Rafacho Badoco |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 16/18045-9 - Study of Hantzsch multicomponent reaction for the synthesis of new dipeptidyl peptidase 4 (DPP-4) inhibitors for treatment of type II Diabetes |
| Grantee: | Mirela Inês de Sairre |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 16/24456-1 - Monoketo enone curcuminoids the treatment of schistosomiasis: an pre-clinical evaluation of schistosomicidal activity |
| Grantee: | Lizandra Guidi Magalhães |
| Support Opportunities: | Regular Research Grants |