Synthesis and antimicrobial activity of a new class of azoimidazoles

Abstract

The emergence of infectious diseases caused by new pathogens or multidrug-resistant (MDR) strains has been a global health threat over the last decades.1 These infections are among the most severe healthcare problems and have been associated to several deaths and heavy economic burden per year.2,3 The imidazole ring is present in several natural and synthetic molecules with biological activity namely on effective antimicrobial agents, which make it a vital anchor for the development of new therapeutic molecules in this field.4 Furthermore, amidrazones are known for their high reactivity thus being useful intermediates for the synthesis of compounds with a wide range of biological activities including antimicrobial. The amidrazone derivatives have been applied in different subjects of chemistry, specifically in the synthesis of azo molecules.5 In a previous work, novel imidazole-based 5-aminoimidazole-4-carboxamidrazones were prepared and exhibited potent antimicrobial activity against C. krusei and C. albicans.6 Further biological studies to elucidate the action mechanism revealed an interesting relationship between the antimicrobial activity and total intracellular ROS production by the yeasts.7 As these carboxamidrazones had previously evidenced a particular susceptibility to the presence of oxygen, all of these results combined prompted us to study the reactivity of 5-aminoimidazole-4-carboxamidrazones in the presence of different oxidant and antioxidant agents. Here, we present results of the electrochemical characterization by cyclic voltammetry to elucidate the oxidation mechanism of these compounds, and the results of the attempts performed to oxidize amidrazones in order to obtain the corresponding azoimidazoles. These products were fully characterized by NMR spectroscopy (including 1H RMN, D2O shake, 13C RMN, HMQC, HMBC and NOE techniques), mass spectroscopy, ATR-FTIR, melting point and elemental analysis. The antimicrobial activity of these new products has been also evaluated and highly promising results were obtained. All the results will be presented and discussed.