Synthesis, Molecular Docking Analysis, and Evaluation of Antibacterial and Antioxidant Properties of Stilbenes and Pinacol of Quinolines

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.

[1]  R. Eswaramoorthy,et al.  Synthesis and Antibacterial, Antioxidant, and Molecular Docking Analysis of Some Novel Quinoline Derivatives , 2020 .

[2]  K. Chibale,et al.  Synthesis and biological evaluation of novel quinoline-piperidine scaffolds as antiplasmodium agents , 2020, European journal of medicinal chemistry.

[3]  C. Fishwick,et al.  New insights into the binding mode of pyridine-3-carboxamide inhibitors of E. coli DNA gyrase. , 2019, Bioorganic & medicinal chemistry.

[4]  S. Levene,et al.  Kinetic pathways of topology simplification by Type-II topoisomerases in knotted supercoiled DNA , 2018, bioRxiv.

[5]  A. Zarghi,et al.  Synthesis and biological evaluation of quinoline analogues of flavones as potential anticancer agents and tubulin polymerization inhibitors. , 2016, European journal of medicinal chemistry.

[6]  Merve Nenni,et al.  Synthesis and evaluation of antioxidant activity of new quinoline-2-carbaldehyde hydrazone derivatives: bioisosteric melatonin analogues , 2016, Journal of enzyme inhibition and medicinal chemistry.

[7]  B. Dave,et al.  Synthesis and antimicrobial activity of novel quinoline derivatives bearing pyrazoline and pyridine analogues , 2016, Medicinal Chemistry Research.

[8]  J. T. Staley,et al.  Classification of Procaryotic Organisms and the Concept of Bacterial Speciation , 2015 .

[9]  C. Len,et al.  Selective Pinacol Coupling on Regeneratable Supported Acids in Sole Water. , 2015, The Journal of organic chemistry.

[10]  P. P. Thankachan,et al.  Theoretical study of the Wittig reaction of cyclic ketones with phosphorus ylide , 2015, Journal of Molecular Modeling.

[11]  D. Kitts,et al.  Antioxidant Property of Coffee Components: Assessment of Methods that Define Mechanisms of Action , 2014, Molecules.

[12]  Peng-Fei Wang,et al.  Design, synthesis, and evaluation of novel fluoroquinolone-flavonoid hybrids as potent antibiotics against drug-resistant microorganisms. , 2014, European journal of medicinal chemistry.

[13]  M. Adrian,et al.  Antimicrobial Activity of Resveratrol Analogues , 2014, Molecules.

[14]  M. G. Bogdanov,et al.  A novel one-pot synthesis and preliminary biological activity evaluation of cis-restricted polyhydroxy stilbenes incorporating protocatechuic acid and cinnamic acid fragments. , 2013, European journal of medicinal chemistry.

[15]  B. Pokhrel,et al.  Emerging threat of multidrug resistant bugs – Acinetobacter calcoaceticus baumannii complex and Methicillin resistant Staphylococcus aureus , 2013, BMC Research Notes.

[16]  Betul Tekiner,et al.  Recent studies of antioxidant quinoline derivatives. , 2013, Mini reviews in medicinal chemistry.

[17]  Wentao Wei,et al.  Efficient synthesis of natural polyphenolic stilbenes: resveratrol, piceatannol and oxyresveratrol. , 2010, Chemical & pharmaceutical bulletin.

[18]  Mamdouh M. Ali,et al.  Synthesis of New Quinoline Derivatives as Inhibitors of Human Tumor Cells Growth , 2010, Archiv der Pharmazie.

[19]  S. Memon,et al.  Synthesis, characterization and investigation of antioxidant activity of cobalt–quercetin complex , 2008 .

[20]  Li-he Zhang,et al.  Rapid Synthesis of Iminosugar Derivatives for Cell‐Based In Situ Screening: Discovery of “Hit” Compounds with Anticancer Activity , 2007, ChemMedChem.

[21]  A. Dinçel,et al.  Penetration of second-, third-, and fourth-generation topical fluoroquinolone into aqueous and vitreous humour in a rabbit endophthalmitis model , 2007, Eye.

[22]  E. Barreiro,et al.  Molecular hybridization: a useful tool in the design of new drug prototypes. , 2007, Current medicinal chemistry.

[23]  J. Polanski,et al.  Investigating biological activity spectrum for novel quinoline analogues. , 2007, Bioorganic & medicinal chemistry.

[24]  B. Kędzia,et al.  Synthesis and antimicrobial activity of new (E)-4-[piperidino (4'-methylpiperidino-, morpholino-) N-alkoxy]stilbenes. , 2006, European journal of medicinal chemistry.

[25]  李真,et al.  Reduction and Coupling Reaction of Carbonyl Compounds by Aluminum Powder and a Small Amount of Oxalic Acid in Water , 2006 .

[26]  M. Mahran,et al.  Synthesis of Some New Antimicrobial Thiadiazolyl and Oxadiazolyl Quinoline Derivatives , 2005, Medicinal Chemistry Research.

[27]  Thomas D. Y. Chung,et al.  A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays , 1999, Journal of biomolecular screening.

[28]  E Bergogne-Bérézin,et al.  Acinetobacter spp. as nosocomial pathogens: microbiological, clinical, and epidemiological features , 1996, Clinical microbiology reviews.

[29]  G. C. Maikap,et al.  Pinacolization and reduction of aromatic carbonyls with aluminium–KOH , 1996 .

[30]  J. Khurana,et al.  Rapid pinacolization of carbonyl compounds with aluminium-KOH , 1994 .

[31]  J. Bosso,et al.  Norfloxacin: A Quinoline Antibiotic , 1986, Drug intelligence & clinical pharmacy.

[32]  O. Meth–Cohn,et al.  A versatile new synthesis of quinolines and related fused pyridines , 1979 .

[33]  M. M. Shemyakin,et al.  The stereochemistry of the Wittig reaction with non-stabilized and semistabilized ylids☆ , 1967 .

[34]  W. Bachmann,et al.  THE REDUCING ACTION OF A MIXTURE OF MAGNESIUM IODIDE (OR BROMIDE) AND MAGNESIUM ON AROMATIC KETONES. PROBABLE FORMATION OF MAGNESIUM SUBIODIDE (OR SUBBROMIDE) , 1927 .