Active Quinolinequinones against Methicillin‐Resistant Staphylococcus spp

Abstract

Serious bacterial infections could be caused by Gram-positive microorganisms, in particular methicillinresistant Staphylococcus aureus and Staphylococcus epidermidis. Aiming to address this challenging issue by developing the potent and selective antimicrobial lead structures against methicillin-resistant Staphylococcus spp., herein, we report in vitro evaluation of quinolinequinones (QQ1-QQ10) against the Gram-negative and Gram-positive strains using the broth microdilution technique. The design principle of the quinolinequinones was based on the variation of the structures attached to the 1,4-quinone moiety and substituent(s) within amino phenyl moiety. A series of ten quinolinequinones displayed activity mainly against the Gram-positive strains with a minimal inhibitory concentration (MIC = 1.22-1250 mg/L) within the Clinical and Laboratory Standards Institute (CLSI) levels. Interestingly, QQ3, QQ5, and QQ6 displayed equal antibacterial inhibitory activity against S. aureus (MIC = 1.22 mg/L), respectively, to the standard positive control Cefuroxime-Na. QQ2, QQ3, and QQ5 had the best inhibitory activity with the MIC value of 1.22 mg/L (4-fold more potent compared reference standard Cefuroxime) against S. epidermidis. On the other hand, QQ3 was the most effective quinolinequinone against fungi, in particular C. albicans. The identified lead quinolinequinones (QQ3 and QQ5) with a comprehensive analysis of structure-activity relationships and further studies showed high activity against methicillin-resistant Staphylococcus spp. It is worth noting that the isopropyl group has importance for excellent bioactivity. Remarkably, the in vitro antibiofilm and bactericidal activities (each of 32 clinically obtained strains of Grampositive bacteria) of the selected two quinolinequinones (QQ3 and QQ5) have been evaluated for the mode of action in addition to the time-kill curve study.

Promising Antibacterial and Antifungal Agents Based on Thiolated Vitamin K3 Analogs: Synthesis, Bioevaluation, Molecular Docking

“…Biofilm attachment and inhibition of biofilm formation assays were performed by the previously described method with some modifications [ 36 ]. For biofilm attachment, an overnight culture of strong, biofilm-producing clinically MRSA isolate was made, which was diluted 1/50 to obtain 1 × 10 6 –1 × 10 7 CFU/200 mL for bacteria in TSB supplemented with 1% glucose.…”

“…A key aspect of the biological activity in our previous studies is the certain chemical modifications of 1,4-quinone moiety. Naphthoquinones [ 19 , 32 , 33 , 34 , 35 ], quinolinequinones [ 27 , 30 , 36 , 37 ], and dimethylbenzoquinones [ 28 , 38 , 39 ] are the most widely used motifs belonging to the quinone family, being biologically important lead structures, which have been extensively used over the years [ 40 , 41 ]. Some of these C2- and/or C2C3-thiolated 1,4-quinones with different side groups were more potent than the reference drug(s).…”

Chemistry, Biosynthesis and Pharmacology of Streptonigrin: An Old Molecule with Future Prospects for New Drug Design, Development and Therapy

“…Its biosynthetic pathway has also been proposed by Wang et al 39 Overall, our findings from this review may provide new insights for the further development of novel quinoline-based drug molecules for the treatment of various disorders. [40][41][42][43][44][45][46] Challenges and Future Prospects for Streptonigrin in New Drug Design,…”