Abstract
Emergence of antimicrobial resistance to standard commercial drugs has become a critical public health concern worldwide. Hence, novel antimicrobials with improved biological activities are urgently needed. In this regard, a series of quinoline-stilbene derivatives were synthesized from substituted quinoline and benzyltriphenylphosphonium chloride using Wittig reaction. Furthermore, a novel pinacol of quinoline was synthesized by pinacolinazation of 2-methoxyquinoline-3-carbaldehyde which was achieved by aluminum powder-potassium hydroxide reagent combination at ambient temperature in methanol. The structures of the synthesized compounds were established based on their spectral data. The antibacterial activities of the synthesized compounds were evaluated in vitro by the paper disc diffusion method against two Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) and two Gram-negative bacteria (Escherichia coli and Salmonella typhimurium). The best activity was displayed by compound 19 against E. coli with an inhibition zone of 16.0 ± 0.82 mm and 14.67 ± 0.94 mm at 500 and 250 μg/mL, respectively. This is close to ciprofloxacin which is used as a positive control. The results of in silico molecular docking evaluation of the compounds against E. coli DNA gyraseB were in good agreement with the in vitro antibacterial analysis. Compounds 19 (−6.9 kcal/mol) and 24 (−7.1 kcal/mol) showed the maximum binding affinity close to ciprofloxacin (−7.3 kcal/mol) used as positive control. Therefore, the antibacterial activity displayed by these compounds is encouraging for further investigation to improve the activities of quinoline-stilbenes by incorporating various bioisosteric groups in one or more positions of the phenyl nuclei for their potential pharmacological use. Findings of the DPPH radical scavenging assay indicated that some of the quinolone stilbenes and pinacol possess moderate antioxidant properties compared to ascorbic acid used as a natural antioxidant.
Highlights
Treatment of infections caused by a variety of microbes including bacteria, viruses, and fungi has been a serious challenge. e problem is exacerbated by the emergence of multidrug microbial resistance to standard commercial drugs. e World Health Organization (WHO) has considered this antimicrobial drug resistance and the diminishing number of active antimicrobial drugs to be one of the greatest threats to human health
Fluoroquinolones were known for their broad-spectrum antimicrobial activities and structural modifications that have resulted in the development of the first- to fifth-generation fluoroquinolone drugs [14, 15]
Synthesis. 2-Chloroquinoline-3-carbaldehyde and 2chloro-8-methylquinoline-3-carbaldehyde were prepared according to the literature report [21]. e various 2substituted quinoline-3- carbaldehyde intermediates that were used in the present work were prepared by the methods that our research team reported previously [22]. e synthesized compounds and the synthetic procure used for each synthesis are summarized in the following tables (Tables 1–6)
Summary
Treatment of infections caused by a variety of microbes including bacteria, viruses, and fungi has been a serious challenge. e problem is exacerbated by the emergence of multidrug microbial resistance to standard commercial drugs. e World Health Organization (WHO) has considered this antimicrobial drug resistance and the diminishing number of active antimicrobial drugs to be one of the greatest threats to human health. Fluoroquinolones were known for their broad-spectrum antimicrobial activities and structural modifications that have resulted in the development of the first- to fifth-generation fluoroquinolone drugs [14, 15]. Stilbenes are another class of biologically active compounds existing in two isomeric forms: (E)- stilbene (transstilbene) and (Z)- stilbene (cis-stilbene) (Figure 1) [16]. Us, due to their useful applications in various fields, scientists pay much attention to the modification of quinolines and stilbenes Noteworthy in this regard is the emergence of new drugs with hybrid molecular architectures possessing better pharmacological properties than small molecules. It is rational to anticipate better bioactivity from a bigger scaffold developed by conjugating the phenyl ring to the quinoline nucleus which has wider sites for suspending different bioisosteres
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