Synthesis and biological evaluation of novel imidazolidine derivatives as candidates to schistosomicidal agents

ABSTRACT Introduction: Schistosomiasis is an infectious parasitic disease caused by trematodes of the genus Schistosoma, which threatens at least 258 million people worldwide and its control is dependent on a single drug, praziquantel. The aim of this study was to evaluate the anti-Schistosoma mansoni activity in vitro of novel imidazolidine derivatives. Material and methods: We synthesized two novel imidazolidine derivatives: (LPSF/PTS10) (Z)-1-(2-chloro-6-fluorobenzyl)-4-(4-dimethylaminobenzylidene)-5-thioxoimidazolidin-2-one and (LPSF/PTS23) (Z)-1-(2-chloro-6-fluoro-benzyl)-5-thioxo-4-(2,4,6-trimethoxy-benzylidene)-imidazolidin-2-one. The structures of two compounds were determined by spectroscopic methods. During the biological assays, parameters such as motility, oviposition, mortality and analysis by Scanning Electron Microscopy were performed. Results: LPSF/PTS10 and LPSF/PTS23 were considered to be active in the separation of coupled pairs, mortality and to decrease the motor activity. In addition, LPSF/PTS23 induced ultrastructural alterations in worms, after 24 h of contact, causing extensive erosion over the entire body of the worms. Conclusion: The imidazolidine derivatives containing the trimetoxy and benzylidene halogens showed promising in vitro schistosomicidal activity.

Activity Anti-Inflammatory and in silico Study of New Thiazolidinedione Derivatives.

Aims: Evaluation of the anti-inflammatory properties of new thiazolidine-2,4-diones derivatives. Study Design: Study the effects of new thiazolidine-2,4-diones derivatives on the inflammatory process. Place and Duration of Study: Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), between June 2011 and July 2012. Methodology: Compounds thiazolidine-2,4-diones were tested for anti-inflammatory activity by air pouch model. Swiss albino mice were used for the study. Air cavities were produced by subcutaneous injection of 2.5 mL of sterile air into the intrascapular area of the back. An additional 2.5 mL of air was injected into the cavity every 3 days to keep the space open. Seven days after the initial air injection, 1 mL of a 1% solution of carrageenan dissolved in saline was injected directly into the pouch to produce an inflammatory response. The compoundsthiazolidine-2,4-diones and standard piroxicam were tested at doses of 3 mg/kg body weight. The total number of polymorphonuclear leukocytes (PMNL) was countedusing an improved. Results: The results support the use of these derivatives in inflammatory process. Among the compounds tested the ones that showed a greater effect in inhibiting the migration of neutrophils were the 3a, 3b, 3c, 3d and 3e. The anti-inflammatory effects showed by 3a-j were promising, probably due to the duality of action on PPAR alpha and gamma. Conclusion: In conclusion, this study has shown that the thiazolidine derivatives do possess significant anti-inflammatory effects in laboratory animals. The exact mechanism and the bioactive principles responsible for these actions remain to be explained.