Síntese e avaliação antimicrobiana de novos híbridos contendo eugenol e o núcleo 1,2,4- oxadiazol

Abstract

In the constant search for new pharmacological compounds, molecular hybridization is a consecrated tool in medicinal chemistry for which two or more pharmacophoric groups are combined to create a new compound called hybrid. It is expected that this hybrid maintains the characteristics of the original compounds, showing improvements in its pharmacological action. In this sense, in this work we report the synthesis of an unprecedented molecular hybrid formed by eugenol and the 1,2,4-oxadiazole nucleus and the evaluation of its antibacterial activity. Eugenol has been applied for quite some time as a natural-based antimicrobial agent, while the 1,2,4-oxadiazole nucleus is a compound that possesses biological properties and is present in various commercially available drugs. Thus, initially they synthesized different arylamidoximes with yields that varied from 78 to 87%. Submission of benzamidoxime to the reaction of O- acylation with acetyl 2-chlorochloride followed by thermal cyclodehydration raised 5- (chloromethyl)-3-phenyl-1,2,4-oxadiazole (4) in a yield of 80%. From the synthetic strategy developed, it was possible to obtain the desired hybrid compound with a yield of 70% by means of the nucleophilic substitution reaction between eugenol (1), fragment A, and 5-(chloromethyl)-3-phenyl-1,2 ,4-oxadiazole (4), fragment B. As structures two synthesized compounds were confirmed by magnetic resonance and mass spectrometry. After the synthesis of the molecular hybrid, it was subjected to antibacterial evaluation against two gram-positive bacteria and showed moderate activity against the S. aureus and S. Pyogenese bacteria with a MIC of 1000 μg/mL. Therefore, the results obtained show that the new synthesized structure is auspicious for the development of new hybrids with therapeutic potential