Synthesis, evaluation of thymidine phosphorylase and angiogenic inhibitory potential of ciprofloxacin analogues: Repositioning of ciprofloxacin from antibiotic to future anticancer drugs

Shahzad, Sohail Anjum; Sarfraz, Ayesha; Yar, Muhammad; Khan, Zulfiqar Ali; Naqvi, Syed Ali Raza; Naz, Sadia; Khan, Nazeer Ahmad; Farooq, Umar; Batool, Razia; Ali, Muhammad

doi:10.1016/j.bioorg.2020.103876

Cited by 6 publications

(3 citation statements)

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“…In the current study, we decided to modify the structural framework of dihydropyridines and pyridines by introducing a range of moieties to accomplish interesting small heterocycles with a high inhibitory activity of alkaline phosphatases and cancer cell lines (HeLa and MCF-7). We have learned from our previous studies on the development of anticancer agents [ 47 , 48 , 49 , 50 , 51 , 52 , 53 ] that the potential of inhibitory activity can be enhanced through the incorporation of bulky groups with various spacers. Furthermore, pro-apoptotic behavior and cell cycle arrests were performed to assess the anticancer potential of the synthesized compounds.…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Novel Dihydropyridine and Pyridine Analogs as Potent Human Tissue Nonspecific Alkaline Phosphatase Inhibitors with Anticancer Activity: ROS and DNA Damage-Induced Apoptosis

et al. 2022

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Small molecules with nitrogen-containing scaffolds have gained much attention due to their biological importance in the development of new anticancer agents. The present paper reports the synthesis of a library of new dihydropyridine and pyridine analogs with diverse pharmacophores. All compounds were tested against the human tissue nonspecific alkaline phosphatase (h-TNAP) enzyme. Most of the compounds showed excellent enzyme inhibition against h-TNAP, having IC50 values ranging from 0.49 ± 0.025 to 8.8 ± 0.53 µM, which is multi-fold higher than that of the standard inhibitor (levamisole = 22.65 ± 1.60 µM) of the h-TNAP enzyme. Furthermore, an MTT assay was carried out to evaluate cytotoxicity against the HeLa and MCF-7 cancer cell lines. Among the analogs, the most potent dihydropyridine-based compound 4d was selected to investigate pro-apoptotic behavior. The further analysis demonstrated that compound 4d played a significant role in inducing apoptosis through multiple mechanisms, including overproduction of reactive oxygen species, mitochondrial dysfunction, DNA damaging, and arrest of the cell cycle at the G1 phase by inhibiting CDK4/6. The apoptosis-inducing effect of compound 4d was studied through staining agents, microscopic, and flow cytometry techniques. Detailed structure–activity relationship (SAR) and molecular docking studies were carried out to identify the core structural features responsible for inhibiting the enzymatic activity of the h-TNAP enzyme. Moreover, fluorescence emission studies corroborated the binding interaction of compound 4d with DNA through a fluorescence titration experiment.

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Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Novel Dihydropyridine and Pyridine Analogs as Potent Human Tissue Nonspecific Alkaline Phosphatase Inhibitors with Anticancer Activity: ROS and DNA Damage-Induced Apoptosis

et al. 2022

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“…Most of the new ciprofloxacin analogs showed good inhibitory activity against thymidine phosphorylase with IC50 range, 39.71-161.89 μM, compared to the reference, 7-deazaxanthine with IC50, 37.82 μM. Additionally, ciprofloxacin-based inhibitor 97 is the most potent derivative among this series with IC50, 39.71 μM [128]. New series of 3,7-bis-benzylidenes derivatives of ciprofloxacin have been synthesized and evaluated for their antitumor activities.…”

Section: Modifications Of Fluoroquinolones At 3 and 7positionmentioning

confidence: 99%

Recent Strategies in Design of Antitumor and Antibacterial Fluoroquinolones

Samir

Ramadan

Hamed

et al. 2021

Journal of advanced Biomedical and Pharmaceutical Sciences

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Fluoroquinolones are known widely used synthetic antibacterial agents. Generally, there were some obstacles associated with their therapeutic use. Moreover, many research studies all over the world proved the variable biological effects of fluoroquinolones such as antituberculosis, anticancer, or even antiviral activities. The current review is focused on modifications that occurred in the fluoroquinolone scaffold for their repositioning from antibacterial into anticancer agents especially modifications at C-7 or at the carboxylic C-3 groups. In addition, it includes the recent research studies carried out to improve the potency, spectrum of activity, or pharmacokinetics of antibacterial fluoroquinolones. Hence, this review may be useful for researchers in the design and synthesis of new fluoroquinolones with improved biological activities.

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“…These immobilized particles can be directly use to heal a disease or to modify cell and molecule on to the targeted areas. Immobilization by NPs is a significant area in biotechnology which offer several different kinds of supports such as nanofibers, nanoflowers and magnetic nanoparticles to hold enzymes for particular function in living system [14][15][16]. Presently, various NPs are being used for immobilization of enzymes [17].…”

mentioning

confidence: 99%

Biomedical uses of Enzymes Immobilized by Nanoparticles

Naqvi¹

2022

Nanomaterial-Supported Enzymes

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Immobilized enzymes are now a significant and appropriate area of modern technologies. Immobilization of enzymes on nanoparticles (NPs) especially magnetic nanoparticles (MNPs) not only increase the stability of the enzymes by protecting the active site but also facilitates the separation mode. Immobilized technology is considered effective in context of running cost to exercise immobilized enzymes technique. Nowadays, variety of magnetic nanoparticles are available such as chitin-chitosan magnetic nanoparticles, Fe3O4 magnetic nanoparticles, bacteriophages T4 capsid novozym-435 etc. which are quite fit for loading enzymes and to use fruitfully. The main focus in this piece of work is that how immobilized enzymes are helpful in different biomedical uses and what kind of enzymes and nanoparticles could be hyphenated to take advantage in health care sectors. Different method of enzymes immobilization will also be discussed in details including both physical methods and chemical methods of loading enzymes on nanoparticles.

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Synthesis, evaluation of thymidine phosphorylase and angiogenic inhibitory potential of ciprofloxacin analogues: Repositioning of ciprofloxacin from antibiotic to future anticancer drugs

Cited by 6 publications

References 74 publications

Design, Synthesis, and Biological Evaluation of Novel Dihydropyridine and Pyridine Analogs as Potent Human Tissue Nonspecific Alkaline Phosphatase Inhibitors with Anticancer Activity: ROS and DNA Damage-Induced Apoptosis

Design, Synthesis, and Biological Evaluation of Novel Dihydropyridine and Pyridine Analogs as Potent Human Tissue Nonspecific Alkaline Phosphatase Inhibitors with Anticancer Activity: ROS and DNA Damage-Induced Apoptosis

Recent Strategies in Design of Antitumor and Antibacterial Fluoroquinolones

Biomedical uses of Enzymes Immobilized by Nanoparticles

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