Synthesis and Biological Evaluation of Bicyclic Pyrazolines with Promising Antimicrobial Activities

TL;DR

Scientists created new bicyclic pyrazoline compounds using flow technology and found they effectively inhibit drug-resistant bacteria.

Contribution

A new class of bicyclic pyrazolines with potent antimicrobial activity against multidrug-resistant bacteria is synthesized and evaluated.

Findings

Bicyclic pyrazolines show low MIC values (0.5–4 μg mL−1) against drug-resistant Staphylococcus and Enterococcus species.

Halogenated aryl rings enhance antimicrobial potency and drug-like properties of the compounds.

The compounds exhibit favorable physicochemical and pharmacokinetic profiles with low predicted toxicity.

Abstract

The efficient photochemical synthesis of bicyclic pyrazolines using flow technology as well as the subsequent antimicrobial evaluation of these scaffolds is reported. Low minimal inhibitory concentration values of 0.5–4 μg mL−1 are found against a series of multidrug resistant bacterial strains including different Staphylococcus and Enterococcus genera species. The lead compound, which is decorated by a halogenated aryl ring system, appears to be bacteriostatic and shows excellent physicochemical and pharmacokinetic properties. Due to low levels of predicted toxicity combined with a high level of drug‐likeness, these bicyclic pyrazolines therefore are promising candidates for further studies as antibacterial species.

Continuous flow technology is exploited for the generation of bicyclic pyrazolines via photo‐click reactions. These heterocyclic species contain a valuable 3D scaffold along with a polar succinimide moiety. Subsequent antimicrobial testing reveals that halogenated moieties such as chlorine atoms and trifluoromethoxy groups enhance the potency of these bacteriostatic compounds reaching low minimal inhibitory concentration values (0.5–4 μg mL−1).© 2025 WILEY‐VCH GmbH

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