Effects of substituents on the NMR features of basic bicyclic ring systems of fluoroquinolone antibiotics and the relationships between NMR chemical shifts, molecular descriptors and drug-likeness parameters

Takač, Milena Jadrijević-Mladar

doi:10.2478/v10007-010-0023-x

Cited by 5 publications

(4 citation statements)

References 22 publications

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“…The obtained NMR spectra for DS, Cipro and complexes are shown in Figure 2. Generally, the spectra accorded well with those previously reported [12,13]. Thus, aromatic protons number 1, 2 and 3 in Cipro resonated at 8.7, 7.9 and 7.6, respectively, while protons in DS appeared at 7.50 ppm (protons 1 + 3, d), 7.13 (protons 5 + 7, t), 7.03 (proton 2, t), 6.82 (proton 6, t), and 6.25 (proton 4, d).…”

Section: Nmr Spectrasupporting

confidence: 91%

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: Nmr Spectrasupporting

confidence: 91%

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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“…Generally, spectra of the prepared salts accorded well with those previously reported for their parent compounds, CP and the four organic anions (20). Thus aromatic protons number 2, 5 and 8 in CP (Fig.…”

Section: Characterization Of Productssupporting

confidence: 88%

Preparation, characterization and antimicrobial assessment of selected ciprofloxacin salts

et al. 2020

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The formation of salts is considered a simple strategy to modify the physicochemical properties of active pharmaceutical ingredients. In this study, seven novel binary and ternary organic salts of ciprofloxacin (CP) were prepared with benzoic acid (BA), acetylsalicylic acid (ASA), p-coumaric acid (PCMA) and p-aminosalicylic acid (PASA). They were characterized by spectroscopic techniques and differential scanning calorimetry. Solubility and partition coefficients values were also measured. Evaluation of the antimicrobial activity of the organic salts against Staphylococcus aureus and Staphylococcus epidermidis revealed that most of the new salts had higher antimicrobial activity than CPHCl against both strains. The most active compounds against S. epidermidis and S. aureus were CP-PASA and CPPCMA, resp., which were up to fourteen times more potent than parent CP-HCl. Our findings indicated a strong correlation between the lipophilicity of the formed salts and their antimicrobial activity and showed that an optimum value of lipophilicity (log P = 0.75) seemed to be necessary to maximize the antimicrobial activity. These findings highlighted the improved physical, thermal and antimicrobial properties of the new salts of CP that can aid in providing higher bioavailability than CP-HCl.

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“…In addition, 13 C-NMR chemical shifts are the result of experiment, whereas most of the independent descriptors used to construct QSAR models are estimated values. Only recently, 13 C-NMR chemical shifts were used successfully to study the property-property and property-drug likeness relationships of some fluoroquinolone salts [ 23 ]. Furthermore, the authors are not aware of any QSAR reports on fluoroquinolones that involved the use of 13 C-NMR chemical shifts as 2D descriptors.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, four quantitative structure activity relationship (QSAR) models that describe the antibacterial activity of these compounds against S. aureus and B. subtilis were obtained using Partial least squares (PLS) regression. One important feature of these models was the use of 13 C-NMR data as one of the 2D QSAR descriptors [ 22 , 23 ]. There is always a quest among medicinal chemists to design new antibacterial agents that are effective against resistant strains.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Antibacterial Evaluation and QSAR of α-Substituted-N4-Acetamides of Ciprofloxacin and Norfloxacin

et al. 2014

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Twenty six α-substituted N4-acetamide derivatives of ciprofloxacin (CIPRO) and norfloxacin (NOR) were synthesized and assayed for antibacterial activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Bacillus subtilis. The derivatives were primarily more active against Gram-positive bacteria. The CIPRO derivatives, CD-7 (Ar = 3-chlorophenyl), CD-9 (Ar = 2-pyrimidyl) and CD-10 (α-phenyl, Ar = 2-pyrimidyl), exhibited lower MIC values, 0.4–0.9 μM, against Staphylococcus aureus than CIPRO, while only compound CD-10 exhibited better activity, 0.1 μM, against Bacillus subtilis than CIPRO. In addition, compounds CD-5 (Ar = 2-methoxyphenyl), CD-6 (α-phenyl, Ar = 2-methoxyphenyl), CD-7 (Ar = 3-Chlorophenyl), CD-8 (α-phenyl, Ar = 3-chlorophenyl) and CD-9 (Ar = 2-pyrimidyl) showed MIC values below 1.0 μM against this strain. The NOR derivatives showed lower activity than NOR itself against Staphylococcus aureus, although ND-6 (α-phenyl, Ar = 2-methoxyphenyl) and ND-7 (Ar = 3-chlorophenyl) showed MIC values less than 2 μM. Two NOR derivatives, ND-7 and ND-6, exhibited MIC values of 0.7 and 0.6, respectively, which were comparable to that of NOR against Bacillus subtilis, while compounds ND-8 (α-phenyl, Ar = 3-chlorophenyl) and ND-10 (α-phenyl, Ar = 2-pyrimidyl) exhibited MIC values less than 1.0 μM against the same strain. QSAR revealed that while polarity is the major contributing factor in the potency against Staphylococcus aureus, it is balanced by lipophilicity and electron density around the acetamide group. On the other hand, electron density around the introduced acetamide group is the major determining factor in the activity against Bacillus subtilis, with a lesser and variable effect for lipophilicity.

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Effects of substituents on the NMR features of basic bicyclic ring systems of fluoroquinolone antibiotics and the relationships between NMR chemical shifts, molecular descriptors and drug-likeness parameters

Cited by 5 publications

References 22 publications

Studies on the interaction between ciprofloxacin hydrochloride and diclofenac sodium

Studies on the interaction between ciprofloxacin hydrochloride and diclofenac sodium

Preparation, characterization and antimicrobial assessment of selected ciprofloxacin salts

Synthesis, Antibacterial Evaluation and QSAR of α-Substituted-N4-Acetamides of Ciprofloxacin and Norfloxacin

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