Antimicrobial Evaluation of New Pyrazoles, Indazoles and Pyrazolines Prepared in Continuous Flow Mode

Abstract

Multi-drug resistant bacterial strains (MDR) have become an increasing challenge to our health system, resulting in multiple classical antibiotics being clinically inactive today. As the de-novo development of effective antibiotics is a very costly and time-consuming process, alternative strategies such as the screening of natural and synthetic compound libraries is a simple approach towards finding new lead compounds. We thus report on the antimicrobial evaluation of a small collection of fourteen drug-like compounds featuring indazoles, pyrazoles and pyrazolines as key heterocyclic moieties whose synthesis was achieved in continuous flow mode. It was found that several compounds possessed significant antibacterial potency against clinical and MDR strains of the Staphylococcus and Enterococcus genera, with the lead compound (9) reaching MIC values of 4 µg/mL on those species. In addition, time killing experiments performed on compound 9 on Staphylococcus aureus MDR strains highlight its activity as bacteriostatic. Additional evaluations regarding the physiochemical and pharmacokinetic properties of the most active compounds are reported and showcased, promising drug-likeness, which warrants further explorations of the newly identified antimicrobial lead compound.

Insights into the eradication of drug resistant Staphylococcus aureus via compound 6-nitrobenzo[cd]indole-2(1H)-ketone

“…11,12 In order to handle the more and more severe problem of drug resistance, there is an urgent and ongoing need to find and develop new antibacterial agents against resistant bacteria. 13–17…”

“…11,12 In order to handle the more and more severe problem of drug resistance, there is an urgent and ongoing need to find and develop new antibacterial agents against resistant bacteria. [13][14][15][16][17] Benz[cd]indol-2(1H)-one (Fig. 1) as a significant skeleton is frequently found in pharmaceuticals, natural products and biologically active compounds.…”