Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents

Zhang, Ling; Addla, Dinesh; Jeyakkumar, Ponmani; Wang, Ao; Xie, Dan; Wang, Ya Nan; Zhang, Shao Lin; Geng, Rong Xia; Cai, Gui Xin; Li, Shuo; Zhou, Changchun

doi:10.1016/j.ejmech.2016.01.052

Cited by 96 publications

(37 citation statements)

References 70 publications

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“…Synthesis of monosubstituted o-phenylenediamines (7,9,11) and chloromethyl benzimidazoles (8, 10,12):I ntermediates 7-12 were prepared according to procedures reported in the literature, starting from o-phenylenediamine. [12,42] Synthesis of 4a:Am ixture of 3 (500 mg, 1.854 mmol), potassium carbonate (256 mg, 1.854 mmol), and sodium iodide (278 mg, 1.854 mmol) in acetonitrile (10 mL) was stirred at 70 8Cf or 0.5 h. After the mixture was cooled to room temperature, compound 8a (361 mg, 1.854 mmol) was added.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…[6][7][8] However, the overuse of quinolones to manage bacterial infections has led to the evolution and widespread distribution of resistant strains,s uch as Streptococcus pneumoniae, Escherichia coli,a nd Staphylococcus aureus. [12,13] Accordingly, it is ap romising strategy that azole rings were introduced into the N1 position of quinolones to strengthen the bindinga ffinity and overcome resistance, because azole rings could bind with DNA, enzymes,a nd receptors in organisms through variousw eaki nteractions, such as coordination bonds, hydrogen bonds, p-p stacking, and the hydrophobic effect. Particularly,a ltera-tions in the conserved ParC helix a4 residues of the topoisomerase IV-DNA complex, positioned in close proximity to the groups at the N1 positiono fq uinolones, directly weakened the binding affinity between quinolonea ntimicrobials and target enzymes.…”

Section: Introductionmentioning

confidence: 99%

“…Particularly,a ltera-tions in the conserved ParC helix a4 residues of the topoisomerase IV-DNA complex, positioned in close proximity to the groups at the N1 positiono fq uinolones, directly weakened the binding affinity between quinolonea ntimicrobials and target enzymes. [12,13] Accordingly, it is ap romising strategy that azole rings were introduced into the N1 position of quinolones to strengthen the bindinga ffinity and overcome resistance, because azole rings could bind with DNA, enzymes,a nd receptors in organisms through variousw eaki nteractions, such as coordination bonds, hydrogen bonds, p-p stacking, and the hydrophobic effect. [14][15][16] Benzimidazole, with al arge, conjugated, rigid, planar structure, is structurallys imilart op urine nucleoside bases,a nd has been attracting increasing interest in drug design for the development of potentiala ntimicrobiala gents.…”

Section: Introductionmentioning

confidence: 99%

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Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA

et al. 2018

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A series of benzimidazole-quinolone hybrids as new potential antimicrobial agents were designed and synthesized. Bioactive assays indicated that some of the prepared compounds exhibited potent antibacterial and antifungal activities. Notably, 2-fluorobenzyl derivative 5 b (ethyl 7-chloro-6-fluoro-1-[[1-[(2-fluorophenyl)methyl]benzimidazol-2-yl]methyl]-4-oxo-quinoline-3-carboxylate) showed remarkable antimicrobial activity against resistant Pseudomonas aeruginosa and Candida tropicalis isolated from infected patients. Active molecule 5 b could not only rapidly kill the tested strains, but also exhibit low toxicity toward Hep-2 cells. It was more difficult to trigger the development of bacterial resistance of P. aeruginosa against 5 b than that against norfloxacin. Molecular docking demonstrated that 5 b could effectively bind with topoisomerase IV-DNA complexes, and quantum chemical studies theoretically elucidated the good antimicrobial activity of compound 5 b. Preliminary experimental reaction mechanism exploration suggested that derivative 5 b could not intercalate into DNA isolated from drug-resistant P. aeruginosa, but was able to cleave DNA effectively, which might further block DNA replication to exert powerful bioactivities. In addition, compound 5 b is a promising antibacterial agent with membrane disruption abilities.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA

et al. 2018

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“…Global increase of multi‐drug‐resistant (MDR) pathogens including methicillin‐resistant Staphylococci aureus (MRSA), penicillin resistant Streptococcus pneumoniae (PRSP), vancomycin resistant enterrococci (VRE) and intolerance of first line drugs pose serious problem in therapeutics . Throughout the world, millions of people suffer from MDR bacterial infections such as of food poisoning, rheumatic fever, salmonellosis, and diarrhea, however so many people die as a direct consequence of this infection .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Structure‐Activity Relationship and Antimicrobial Evaluation of Methyl‐Substituted Tetrazoloquinoline‐Based Pyrazolinethioamides

et al. 2016

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A new series of pyrazolinethioamide and intermediate chalcone were synthesized from the tetrazoloqunoline molecule and the effect of these compounds on in-vitro growth of microorganisms is studied. In-vitro anti-microbial activity was performed against S.aureus, S.epidermidis, P.mirabilis and E.coli. A number of analogues exhibited potent activity against all the bacterial strains. The SAR results indicate that the thioamide, methoxy group at C-4 of phenyl ring and tetrazole unit play key roles for their bacterial inhibitory effect. This is further supported by the molecular modeling study of the crystal structure of PDB: 4Z7 M with compounds 5 b and 5 g. Compound 5 b showed potent antibacterial activity against S.aureus, S.epidermidis and moderate activity against E.coli with MIC values 6.25, 3.125, and 6.25 mg/mL, respectively. Compound 5 g showed potent antibacterial activity against S.epidermidis with MIC value 3.125 mg/mL but moderate activity against P.mirabilis and E. coli. Most promising compounds were tested for cytotoxic study by MTT assay on HepG2 cell line and the results showed that all the compounds offered remarkable > 70 % viability up to the concentration of 100 mg/mL.

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Synthesis and characterization of Ni (II), Cu (II), Fe (II) and Fe₃O₄ nanoparticle complexes with tetraaza macrocyclic Schiff base ligand for antimicrobial activity and cytotoxic activity against cancer and normal cells

Chaabane

Chahdoura²,

Moslah

et al. 2019

Applied Organom Chemis

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This work describes a simple synthesis of complexes of the type [M(C32H28N4)Cl2], where M = Ni (II), Cu (II) and Fe (II) and a novel complex of magnetite nanoparticle (Fe3O4NP) inside (INS) tetraaza macrocyclic Schiff base ligand (C32H28N4): [Fe3O4NP‐INS‐(C32H28N4)], which was prepared by using a novel co‐precipitation method of coordinated ferric ion (Fe3+) in the complex [Fe(C32H28N4)Cl2] under mild conditions. The synthesized compounds were characterized and compared with a various physic‐chemical techniques like: Fourier transform infrared (FT‐IR), ultraviolet–visible spectroscopic techniques (UV–Vis), 1‐dimensional (1D) 1H‐NMR, 13C‐NMR spectroscopic techniques, mass spectra, Powder X‐ray diffraction (PXRD), Vibrating sample magnetometer (VSM), Scanning electron microscopy (SEM), elemental analysis and molar conductance measurements. Furthermore, the highest saturation magnetization was 26.56 emu.g−1 obtained from [Fe3O4NP‐INS‐(C32H28N4)] (diameter of Fe3O4NPs~20.87 nm) that prove easy separation by an external magnetic field. In vitro screening of all the compounds against different species of bacteria and fungi shows that [Fe3O4NP‐INS‐(C32H28N4)] is effective against the tested strains as compared to the tetraaza macrocyclic ligand and selected complexes. The cytotoxic activity of the all compounds was also examined in 3 human tumor cell lines as U87, MDA‐MB‐231 and LS‐174. The complex [Fe3O4NP‐INS‐(C32H28N4)] shows moderate and strong cytotoxic activity against brain cancer, colon cancer and breast cancer (U87, MDA‐MB‐231 and LS‐174 respectively), without showing cytotoxicity towards peripheral blood mononucleocyte (PBMC) cells.

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Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents

Cited by 96 publications

References 70 publications

Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA

Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA

Synthesis, Structure‐Activity Relationship and Antimicrobial Evaluation of Methyl‐Substituted Tetrazoloquinoline‐Based Pyrazolinethioamides

Synthesis and characterization of Ni (II), Cu (II), Fe (II) and Fe₃O₄ nanoparticle complexes with tetraaza macrocyclic Schiff base ligand for antimicrobial activity and cytotoxic activity against cancer and normal cells

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Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents

Cited by 96 publications

References 70 publications

Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA

Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA

Synthesis, Structure‐Activity Relationship and Antimicrobial Evaluation of Methyl‐Substituted Tetrazoloquinoline‐Based Pyrazolinethioamides

Synthesis and characterization of Ni (II), Cu (II), Fe (II) and Fe3O4 nanoparticle complexes with tetraaza macrocyclic Schiff base ligand for antimicrobial activity and cytotoxic activity against cancer and normal cells

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Product

Resources

About

Synthesis and characterization of Ni (II), Cu (II), Fe (II) and Fe₃O₄ nanoparticle complexes with tetraaza macrocyclic Schiff base ligand for antimicrobial activity and cytotoxic activity against cancer and normal cells