Synthesis of Novel Quinolines with Antibacterial Activity

In recent years, the development of pharmaceuticals and high-value fine chemicals based on heterocycles has sustained strong activity. Discovery of new medicines based on heterocycles remains an ever-important theme. The discovery of novel antimicrobial agents to combat bacterial resistance is crucial, and among the important heterocyclic systems playing a strong role in this process of discovery are the quinolines. Our ongoing research aims at the development of bioactive agents, and in the present study we have prepared some novel quinoline derivatives and assayed their antibacterial activity.
The novel compounds have been synthesized, rigorously characterized and biologically evaluated in continuation of our recent work, as shown in Scheme 1. Thus 4-aminoanisole (1) was heated with ethyl 3-oxobutanoate in ethanol to produce 2. At a temperature of 260 °C, compound 2 underwent thermal cyclization to form compound 3. This was treated with chloroacetic acid to produce compound 4. At a temperature of 170-180°C the reaction between compound 4 and thiocarbohydrazide gave 5, which was the source material for our novel compounds. The reaction of compound 5 with suitable aldehydes in the presence of p-toluenesulfonic acid resulted in the formation of derivatives 6a (80%) and 6b (69%). Aryl isothiocyanates were warmed with compound 5 to yield compounds 7a (81%) and 7b (68%). Finally, 4-methylphenacyl bromide was reacted with compound 5 to give compound 8 (81%).

Our new quinoline derivatives were screened for their antimicrobial activity using ampicillin as a positive control as displayed in Table 1. When comparing substances 6b and 7b to ampicillin, it was observed that they exhibited significant inhibitory activity against both gram-positive and gram-negative strains. The remaining compounds displayed moderate activity.

In summary, five novel quinolines were synthesized, fully characterized and assayed for their antibacterial potency. Among the prepared compounds, two compounds (6b and 7b) showed good potency against the bacterial strains studied, with results equivalent to or slightly better than the control ampicillin.