Synthesis of new trypanocidal agents from the hybridisation of metronidazole and eugenol analogues.

Nitroimidazole compounds are well-known bioactive substances, and the structural activity relationship has been reported whereby the position of the nitro group within the imidazole ring has a large influence on the activity. This study focuses on synthesising new trypanocidal agents from the hybridisation of metronidazole with different natural phenols (eugenol, dihydroeugenol and guaiacol). Two different coupling methodologies have been explored in order to analyse the influence of the connector on bioactivity: i) classic direct esterification (AD compounds) and ii) "click" chemistry using a triazole connector (AC compounds).

Pharmacological potential of new metronidazole/eugenol/dihydroeugenol hybrids against Trypanosoma cruzi in vitro and in vivo.

Aims: From well-delimited immunomodulatory, redox and antimicrobial properties; metronidazole and eugenol were used as structural platforms to assembly two new molecular hybrids (AD06 and AD07), whose therapeutic relevance was analyzed on T. cruzi infection in vitro and in vivo.

Methods: Non-infected, T.

Synthesis of New Hybrid Derivatives from Metronidazole and Eugenol Analogues as Trypanocidal Agents.

Background: The search for new drug compounds is always challenging and there are several different strategies that involve the most varied and creative approaches in medicinal chemistry. One of them is the technique of molecular hybridisation: forming a hybrid compound from two or more pharmacophoric subunits. These hybrids may maintain the characteristics of the original compound and preferably show improvements to its pharmacological action, with reduced side effects and lower toxicity when compared to the original components.