Design, synthesis, and evaluation of novel fluoroquinolone–flavonoid hybrids as potent antibiotics against drug-resistant microorganisms

Xiao, Zhu‐Ping; Wang, Xudong; Wang, Pengfei; Yin, Zhihua; Zhang, Jingwen; Zhang, Lei; Zhou, Jiao; Zhou, Shasha; Ouyang, Hongwei; Lin, Xiao-Yi; Mustapa, Manzira; Reyinbaike, Asaimuguli; Zhu, Hai‐Liang

doi:10.1016/j.ejmech.2014.04.037

Cited by 77 publications

(38 citation statements)

References 36 publications

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“…As regards natural products, in literature there are several studies investigating the promising antimicrobial activity of chemical compounds content in essential oils and medicinal plants, also traditionally used for the treatment of various health disorders [3][4][5] . Both structure and ligand-based virtual screening (SBVS and LBVS) represent alternative and innovative approaches for identifying new compounds, but, until now, in the field of anti-Candida, computational techniques were used only to explain the structureactivity relationships, to design synthetic derivatives for the lead optimization and to display hypothetic mechanisms of action [6][7][8] . LBVS often relies on 3D pharmacophore model that is a set of interactions, or chemical features, aligned in three-dimensional space and developed by two possible approaches: one based on the known X-ray or NMR structure of the receptor, and the other one starting from a set of ligands that are supposed to bind to the same unknown target 9 .…”

Section: Introductionmentioning

confidence: 99%

Identification of new anti-Candida compounds by ligand-based pharmacophore virtual screening

Gidaro

Alcaro

Secci

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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Candida albicans represents the most prevalent microbial population in mucosal and systemic infections, usually confined to severely immunocompromised people. Considering the increase of resistant strains and the demand for new antifungal drugs endowed with innovative mechanism of action, we performed a ligand-based virtual screening in order to identify new anti-Candida compounds. Starting from a large library of natural/semisynthetic products and several published synthesized compounds, three coumarin derivatives were discovered in silico as new hit compounds and submitted to the in vitro assay in order to confirm their predicted biological activity.

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Section: Introductionmentioning

confidence: 99%

Identification of new anti-Candida compounds by ligand-based pharmacophore virtual screening

Gidaro

Alcaro

Secci

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Whole cells accumulation revealed that introduction of naringenin to the fluoroquinolone structure prevents of the hybrid from being the substrate for the efflux pumps. Ciprofloxacin (R 1 = cyclopropyl, X = CH) and sarafloxacin (R 1 = 4F-C 6 H 4 , X = CH) hybrids of naringenin ( 97 ) exhibited greater inhibitory activities than reference ciprofloxacin against the DNA gyrase in DNA supercoiling assay, confirming their strong fluoroquinolone character [172] (Fig. 21).…”

Section: Other Modificationsmentioning

confidence: 98%

Modifications of quinolones and fluoroquinolones: hybrid compounds and dual-action molecules

Fedorowicz

Sączewski

2018

Monatsh Chem

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This review is aimed to provide extensive survey of quinolones and fluoroquinolones for a variety of applications ranging from metal complexes and nanoparticle development to hybrid conjugates with therapeutic uses. The review covers the literature from the past 10 years with emphasis placed on new applications and mechanisms of pharmacological action of quinolone derivatives. The following are considered: metal complexes, nanoparticles and nanodrugs, polymers, proteins and peptides, NO donors and analogs, anionic compounds, siderophores, phosphonates, and prodrugs with enhanced lipophilicity, phototherapeutics, fluorescent compounds, triazoles, hybrid drugs, bis-quinolones, and other modifications. This review provides a comprehensive resource, summarizing a broad range of important quinolone applications with great utility as a resource concerning both chemical modifications and also novel hybrid bifunctional therapeutic agents.Graphical abstract

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“…Fluoroquinolone-favonoid hybrids combine the targeting of gyrase/topoisomerase IV with efflux pump inhibition [85]. The narigenin-ciprofloxacin hybrid showed 8-and 23-fold stronger activity than ciprofloxacin alone when tested against E. coli and S. aureus, respectively [85]. The 3-arylfuran-2(5H)-one pharmacophore-targeting tyrosyl-tRNA synthetase was used to form a hybrid with fluoroquinolone [86].…”

Section: New Gyrb or Gyrb/pare Atpase Inhibitorsmentioning

confidence: 99%

Targeting bacterial topoisomerases: how to counter mechanisms of resistance

Tse‐Dinh

2016

Future Medicinal Chemistry

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DNA gyrase and topoisomerase IV are type IIA bacterial topoisomerases that are targeted by highly effective antibiotics. However, resistance via multiple mechanisms arises to limit the efficacies of these drugs. Continued research on type IIA bacterial topoisomerases has provided novel approaches to counter the most common resistance mechanism for utilization of these proven targets in antibacterial therapy. Bacterial topoisomerase I is being explored as an alternative target that is not expected to show cross-resistance. Dual targeting or combination therapy could be strategies for circumventing the development of resistance to topoisomerase-targeting antibiotics. Bacterial topoisomerases are high-value bactericidal targets that could continue to be exploited for antibacterial therapy, if new tactics to counter resistance can be adopted.

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Design, synthesis, and evaluation of novel fluoroquinolone–flavonoid hybrids as potent antibiotics against drug-resistant microorganisms

Cited by 77 publications

References 36 publications

Identification of new anti-Candida compounds by ligand-based pharmacophore virtual screening

Identification of new anti-Candida compounds by ligand-based pharmacophore virtual screening

Modifications of quinolones and fluoroquinolones: hybrid compounds and dual-action molecules

Targeting bacterial topoisomerases: how to counter mechanisms of resistance

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