Synthesis of new compounds based on Lawsone via a multi-component reaction

Tandem multi-component reactions (MCR) are convergent syntheses that begin with three or more reactants and, preferably, end with only one formed product that contains all of the starting atoms.1 Naphthoquinones play vital roles in several biological processes and are considered to be of great importance in medicinal chemistry. Naphthoquinones are often associated with various biological activities, including anticancer, antibacterial, antimalarial, trypanocidal, tuberculostatic and fungicidal activities.2 Lawsone (1) is a 1,3-dicarbonyl compound that have been extensively used by synthetic organic chemists because of their peculiar chemical structures and their relationships with biologically important natural products. Indeed, this natural product has a large variety of biological activity that has been studied in recent decades and stimulated the synthesis of a large number of synthetic analogues. With this aim in mind and as a further extension of our studies of the chemistry of naphthoquinones, we have prepared a new serie of compounds 5a-i, which are structurally related to lawsone (1), via a fourcomponent reaction using lawsone (1) as a starting material. The resistance phenomenon has allowed bacterial infections to continue emerging more than 50 years after antimicrobials were introduced in clinical practice. This problem shows great interest in the development of new molecules that act as antimicrobials. Gram-positive bacteria can cause infections in patients in the hospital setting and also in the community. In this work we evaluated 32 Gram positive isolates, belonging to genus Staphylococcus, Enterococcus and Streptococcus, resistant and sensitive to the main antimicrobials used for therapy. Bacteria were analyzed by diluting different concentrations of the compound on Muller Hinton agar with subsequent addition of the isolates using the Steers replicator`s. The compound - HM-02 was the most effective because most of the isolates showed minimal inhibitory concentration (MIC) ≤ 256 μg / mL. All methicillin-resistant Staphylococcus aureus (MRSA) showed MIC ≤ 128 μg/mL. It demonstrates this compound is a potential promise as anti-S. aureus.