Synthesis and evaluation of antibacterial and antifungal activities of asymmetric 2-methylimidazole-4,5-dicarboxamide derivatives containing morpholine

Abstract

For several years, heterocycles have been attracted the interest of researchers due to their diverse biological activity, such as antibacterial, antifungal, antidengue properties,… Imidazole and morpholine are two heterocycles that have interesting application in potency, pharmacokinetics, pharmacodynamics… When combined in the same compound, they may generate new compounds with potential bioactivities. Imidazole-4,5-dicarboxamide (I45DC) compounds were synthesized using benzimidazole derivatives as starting material through four-step procedure: oxidation cleavage of 2-methylbenzimidazole, synthesis of pyrazinedione diacide dichloride, amidation of pyrazinedione diacide dichloride, and ring opening pyrazinedione by morpholine. The structures were determined by IR, MS, NMR spectra. The results showed that the derivatives have purity and structure consistent with expectations. Eight asymmetric I45DC compounds were synthesized, all of which were new based on Scifinder in December 2022. The yield of the reactions varies from 23 – 80%, in which the important reaction is the final one with the yield of 23 – 54% varying depending on the position of the substituents. The antibacterial, antifungal, antidengue activitives were screened on five bacterial and two fungi strains. However, they did not exhibit activity againtst tested bacteria and fungi. Nonetheless, the new I45DC compounds help to diversify synthetic compounds.