Synthesis and characterization of N-Mannich based prodrugs of ciprofloxacin and norfloxacin: In vitro anthelmintic and cytotoxic evaluation

Piplani, Mona; Rajak, Harish; Sharma, Prabodh Chander

doi:10.1016/j.jare.2017.06.003

Cited by 29 publications

(14 citation statements)

References 16 publications

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“…Ternary complexes involving metal ions exhibited similar or slightly higher log P values than the 1:1 complexes, which accords with our findings that these complexes form predominantly as 1:1. The hydrophilicity of native Cipro with its consequent poor bioavailability is well known and some approaches have been attempted to overcome that hurdle [15].…”

Section: Discussionmentioning

confidence: 99%

Studies on the interaction between ciprofloxacin hydrochloride and diclofenac sodium

El-Sabawi¹,

Abu-Dahab²,

Bakri³

et al. 2019

Trop. J. Pharm Res

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Purpose: To study the interaction between ciprofloxacin hydrochloride (Cipro) and diclofenac sodium (DS) in the presence and absence of metal ions. Methods: Complexes were prepared in the aqueous phase at different molar ratios (r) of Cipro:DS (ranged from 0.2-2.0). The complexes were characterized by Fourier transform-infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and high pressure liquid chromatography (HPLC). Their properties, i.e., solubility, dissolution and partition coefficient (log P), were studied along with their permeability across Caco-2 cells. Furthermore, the antimicrobial activity of Cipro and its complexes was determined using standard broth dilution method and expressed as minimum inhibitory concentration (MIC). Results: Cipro formed an ion pair with DS. The product was confirmed to be a combination of the two drugs, DS and Cipro, but in a ratio that is dependent on the added amounts of each component (r = 1:1 or 1:2). The 1:1 product was more lipophilic than the individual components leading to a lower aqueous solubility and a higher octanol/water partition coefficient log P (6.7 vs. 0.77). The presence of DS within the dissolution medium appeared to modify the dissolution of Cipro depending on the concentration. Moreover, ternary complexes involving Cipro, DS and metal ions (iron and/or calcium) exhibited improved antimicrobial effect (MIC, 0.016 µg/ml compared to 0.258 µg/ml for Cipro). Caco-2 cell permeation data indicate that the presence of DS significantly improved the apparent permeability coefficient (Papp) of Cipro (20.6 × 10-6 cm/s) which was three times higher than that of free Cipro (p < 0.05). DS also appeared to counteract the well-known negative effect of metal ions on the bioavailability of Cipro. Conclusion: There is a clinically relevant interaction between DS and Cipro at the absorption level as a result of ion pair formation, which might even counteract the negative effect of metals on the absorption of Cipro. These findings should aid the design of new Cipro ion pairs that provide higher bioavailability than free Cipro.

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Section: Discussionmentioning

confidence: 99%

Studies on the interaction between ciprofloxacin hydrochloride and diclofenac sodium

El-Sabawi¹,

Abu-Dahab²,

Bakri³

et al. 2019

Trop. J. Pharm Res

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“…The norfloxacin analogs substituted at N-7 with benzo[d]thiazolyl moiety through butyramide linker were evaluated for the cytotoxic activities against A549, lung cancer cell line. Compound 70 exhibited the highest activity among these derivatives with GI50 of 28.8 μg/ml [104]. Otherwise, the ciprofloxacin derivatives substituted at the N-7 site with 1,3,4-thiadiazol moiety through acetamide linker does not give the expected cytotoxic activities.…”

Section: Modifications Of Fluoroquinolones At 7positionmentioning

confidence: 93%

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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“…Derivatives of ciprofloxacin and norfloxacin substituted at the piperazinyl N‐ 4 with N‐ (benzo[ d ]thiazol‐2‐yl)butyramide substituents were tested for cytotoxicity using the human lung cancer cell lines A549. Compound 14 was the most potent derivative in the series, with GI 50 of 28.8 µg/ml . On the other hand, introducing N ‐(1,3,4‐thiadiazol‐2‐yl)acetamide derivatives to the N terminus of ciprofloxacin and norfloxacin did not offer a benefit for the antitumor activity at a concentration of 10 µM.…”

Section: Fluoroquinolone Derivatives With Anticancer Activitymentioning

confidence: 94%

Towards anticancer fluoroquinolones: A review article

Abdel-AAl

Abdel‐Aziz

Shaykoon

et al. 2019

Archiv der Pharmazie

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Different studies about the anticancer potential of several medically used antibacterial fluoroquinolones have been established. Fluoroquinolone derivatives, like some anticancer drugs, such as doxorubicin, can achieve antitumor activity via poisoning of type II human DNA topoisomerases. Interestingly, structural features required for the anticancer activity of quinolones have been determined. Most of the chemical modifications required to convert antibacterially acting fluoroquinolones into their anticancer analogs were at position 7 and the carboxylic group at position 3. This review highlights the antitumor potential of fluoroquinolones in general and summarizes the chemical modifications carried out on fluoroquinolones to become anticancer agents. Moreover, the review gives a quick recap on metal ion chelates with fluoroquinolones and their substantial role in topoisomerase poisoning and antitumor potential improvement. Hence, it should be highly interesting for researchers attempting to design and synthesize novel anticancer fluoroquinolone candidates. K E Y W O R D S anticancer, DNA topoisomerase, metal ion complexes, quinolones Arch Pharm Chem Life Sci. 2019;352:1800376.wileyonlinelibrary.com/journal/ardp

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Synthesis and characterization of N-Mannich based prodrugs of ciprofloxacin and norfloxacin: In vitro anthelmintic and cytotoxic evaluation

Abstract: Graphical abstract

Cited by 29 publications

References 16 publications

Studies on the interaction between ciprofloxacin hydrochloride and diclofenac sodium

Studies on the interaction between ciprofloxacin hydrochloride and diclofenac sodium

Recent Strategies in Design of Antitumor and Antibacterial Fluoroquinolones

Towards anticancer fluoroquinolones: A review article

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