A Comprehensive Review on Chemical Synthesis and Chemotherapeutic Potential of 3-Heteroaryl Fluoroquinolone Hybrids

Hryhoriv, Halyna; Kovalenko, Sergiy M.; Georgiyants, Marine; Сидоренко, Л. В.; Georgiyants, Victoriya

doi:10.3390/antibiotics12030625

Cited by 8 publications

(1 citation statement)

References 55 publications

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“…Thus, evaluating the acetylated form of histones H3 and/or H4 is considered a good strategy to assess HDAC activity and check whether a candidate drug can act as an HDACi [ 64 , 65 ]. To date, HDAC inhibitory activity has been demonstrated only in FQ hybrids and FQs/HDACi conjugates [ 66 , 67 ]. Interestingly, CIP and NOR increased only acetylated H4 levels in MCF7 and in MDA-MB231 and 5637 cells, respectively.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of the Antineoplastic Effects of New Fluoroquinolones in 2D and 3D Human Breast and Bladder Cancer Cell Lines

Ferrario,

Marras,

Vivona

et al. 2024

Cancers

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Antibacterial fluoroquinolones have emerged as potential anticancer drugs, thus prompting the synthesis of novel molecules with improved cytotoxic characteristics. Ciprofloxacin and norfloxacin derivatives, previously synthesized by our group, showed higher anticancer potency than their progenitors. However, no information about their mechanisms of action was reported. In this study, we selected the most active among these promising molecules and evaluated, on a panel of breast (including those triple-negative) and bladder cancer cell lines, their ability to induce cell cycle alterations and apoptotic and necrotic cell death through cytofluorimetric studies. Furthermore, inhibitory effects on cellular migration, metalloproteinase, and/or acetylated histone protein levels were also evaluated by the scratch/wound healing assay and Western blot analyses, respectively. Finally, the DNA relaxation assay was performed to confirm topoisomerase inhibition. Our results indicate that the highest potency previously observed for the derivatives could be related to their ability to induce G2/M cell cycle arrest and apoptotic and/or necrotic cell death. Moreover, they inhibited cellular migration, probably by reducing metalloproteinase levels and histone deacetylases. Finally, topoisomerase inhibition, previously observed in silico, was confirmed. In conclusion, structural modifications of progenitor fluoroquinolones resulted in potent anticancer derivatives possessing multiple mechanisms of action, potentially exploitable for the treatment of aggressive/resistant cancers.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of the Antineoplastic Effects of New Fluoroquinolones in 2D and 3D Human Breast and Bladder Cancer Cell Lines

Ferrario,

Marras,

Vivona

et al. 2024

Cancers

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Photoisomerization and Light‐Controlled Antibacterial Activity of Fluoroquinolone‐Azoisoxazole Hybrids

Dolai,

Bhunia,

Jana

et al. 2024

ChemBioChem

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Photopharmacology holds a huge untapped potential to locally treat diseases involving photoswitchable drugs to eliminate drugs’ off‐target effects. The growth of this field has created a pressing demand to develop such light‐active drugs. We explored the potential for creating photoswitchable antibiotic hybrids by attaching pharmacophores norfloxacin/ciprofloxacin and azoisoxazole (photoswitch). All compounds exhibited a moderate to a high degree of bidirectional photoisomerization, long thermal cis half‐lives, and impressive photoresistance. Gram‐negative pathogens were found to be insensitive to these hybrids, while against Gram‐positive pathogens, all hybrids in their trans states exhibited antibacterial activity comparable to the parent drugs. Notably, the toxicity of the irradiated hybrid 6 was 2‐fold lower than the nonirradiated trans isomer, indicating that the pre‐inactivated cis–enriched drug can be employed for the site‐specific treatment of bacterial infection using light, which could potentially eliminate the unwanted exposure of toxic antibiotics to both beneficial and untargeted harmful microbes in our body. Molecular docking studies revealed different binding affinity of the cis and trans isomers of 6 with the topoisomerase IV enzyme, due to their different shapes.

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Aniquinazoline B, a Fungal Natural Product, Activates the μ‐Opioid Receptor

Damiescu,

Elbadawi,

Dawood

et al. 2024

ChemMedChem

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The development of new µ‐opioid receptor (MOR) agonists without the undesirable side effects, such as addiction or respiratory depression, has been a difficult challenge over the years. In the search for new compounds, we screened our chemical database of over 40.000 substances and further assessed the best 100 through molecular docking. We selected the top 10 compounds and evaluated them for their biological activity and potential to influence cyclic adenosine monophosphate (cAMP) levels. From the tested compounds, compound 7, called aniquinazoline B, belonging to the quinazolinone alkaloids class and isolated from the marine fungus Aspergillus nidulans, showed promising results, by inhibiting cAMP levels and in vitro binding to MOR, verified through microscale thermophoresis. Transcriptomic data investigation profiled the genes affected by compound 7 and discovered activation of different pathways compared to opioids. The western blot analysis revealed compound 7 as a balanced ligand, activating both p‐ERK1/2 and β‐arrestin1/2 pathways, showing this is a favorable candidate to be further tested.

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A Comprehensive Review on Chemical Synthesis and Chemotherapeutic Potential of 3-Heteroaryl Fluoroquinolone Hybrids

Cited by 8 publications

References 55 publications

Mechanisms of the Antineoplastic Effects of New Fluoroquinolones in 2D and 3D Human Breast and Bladder Cancer Cell Lines

Mechanisms of the Antineoplastic Effects of New Fluoroquinolones in 2D and 3D Human Breast and Bladder Cancer Cell Lines

Photoisomerization and Light‐Controlled Antibacterial Activity of Fluoroquinolone‐Azoisoxazole Hybrids

Aniquinazoline B, a Fungal Natural Product, Activates the μ‐Opioid Receptor

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