Alkylation of 3‐Phenyl‐1<i>H</i>‐pyrazolo[4,3‐<i>c</i>] quinoline: Theoretical Analysis of Regioselectivity

Савченко, Т. И.; Silin, Olexiy V.; Kovalenko, Sergiy M.; Мусатов, Владимир И.; Nikitchenko, V. M.; Ivachtchenko, Alexander V.

doi:10.1080/00397910701227077

Cited by 11 publications

(4 citation statements)

References 9 publications

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“…These issues were the reason to look for other options, mainly for one-step procedure, based on the experimental results for similar researchers [9,11].…”

Section: Discussionmentioning

confidence: 99%

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Structural modification of ciprofloxacin and norfloxacin for searching new antibiotics to combat drug-resistant bacteria

Hryhoriv

Mariutsa

Kovalenko

et al. 2021

SR: PS

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The aim of the work. Among all the representatives of four generations of fluoroquinolones ciprofloxacin (CIPRO) and norfloxacin (NOR) remain widely used and prescribed antibiotics in clinical practice. However, the problem of resistance towards them is gradually increasing. Thus, our investigation is dedicated to chemical modification of C-7 position of Ciprofloxacin and Norfloxacin ring as a promising solution to combat antibiotic resistance and open a pathway towards convenient synthesis of new fluoroquinolones derivatives. Materials and methods. The subjects of the research were N-piperazine-substituted ciprofloxacin and norfloxacin. The methods of molecular docking and organic synthesis were applied in the study. The structures of the obtained compounds were confirmed by 1H NMR, 13C NMR, 19F NMR, LC/MS, IR, UV spectroscopy. The antimicrobial activity was measured by the method of double serial dilutions against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Bacillus subtilis (ATCC 6633), Pseudomonas aeruginosa (ATCC 27853), Candida albicans (NCTC 885-653) and diffusion in agar method against clinical strains. The results. 7-(4-(2-Cyanoacetyl)piperazin-1-yl)-1-R-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acids were synthesized and their structures were confirmed. The obtained compounds showed the antibacterial activity on the reference level for double dilution method and exceeded control for “well” method. Conclusions. The current investigation revealed the promising route for the expanding of the existing fluoroquinolones diversity. Pharmacodynamics and pharmacokinetics changes could be achieved by chemical modifications of C-7 position of the initial ring. Further research utilizing the obtained compounds as starting ones opens a promising way to novel active molecules synthesis and combating the problem of antibiotic resistance

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“…These issues were the reason to look for other options, mainly for one-step procedure, based on the experimental results for similar researchers [9,11].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, continuing our investigations in the area of quinolone chemistry [9][10][11] and using previous synthetic experience we decided to accept such challenging task and find a way to modify Ciprofloxacin and Norfloxacin in order to fight the problem of antibiotic resistance.…”

Section: Introductionmentioning

confidence: 99%

Structural modification of ciprofloxacin and norfloxacin for searching new antibiotics to combat drug-resistant bacteria

Hryhoriv

Mariutsa

Kovalenko

et al. 2021

SR: PS

Self Cite

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“…Thus, hybrids of fluoroquinolones with derivatives of phenylthiazole, quinazoline, thiazolidine, thiadiazole, pyrimidine, dithienylethene, and 1,2,4-triazole are widely described in the literature (Suaifan & Mohammed, 2019;Jia & Zhao, 2021). Our scientific team has been fruitfully working in this direction (Bylov et al, 1999;Silin et al, 2004;Savchenko et al, 2007;Hryhoriv et al, 2022;Vaksler et al, 2022). At the same time, a thorough analysis of literature sources demonstrates that modification of the 3-position of fluoroquinolones is promising and insufficiently researched (Oniga et al, 2018).…”

Section: Chemical Contextmentioning

confidence: 99%

Synthesis, analysis of molecular and crystal structures, estimation of intermolecular interactions and biological properties of 1-benzyl-6-fluoro-3-[5-(4-methylcyclohexyl)-1,2,4-oxadiazol-3-yl]-7-(piperidin-1-yl)quinolin-4-one

et al. 2023

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The title compound, C30H33N4O2F, can be obtained via a two-step synthetic scheme involving 1-benzyl-6-fluoro-4-oxo-7-(piperidin-1-yl)-1,4-dihydroquinoline-3-carbonitrile as a starting compound that undergoes substitution with hydroxylamine and subsequent cyclization with 4-methylcyclohexane-1-carboxylic acid. It crystallizes from 2-propanol in the triclinic space group P\overline{1} with a molecule of the title compound and one of 2-propanol in the asymmetric unit. After the molecular structure was clarified using NMR and LC/MS, the molecular and crystalline arrangements were defined with SC-XRD. A Hirshfeld surface analysis was performed for a better understanding of the intermolecular interactions. One strong (O—H...O) and three weak [C—H...F (intramolecular) and two C—H...O] hydrogen bonds were found. The contributions of short contacts to the Hirshfeld surface were estimated using two-dimensional fingerprint plots showing that O...H/H...O, C...H/H...C and C...C contacts are the most significant for the title compound and O...H for the 2-propanol. The crystal structure appears to have isotropically packed tetramers containing two molecules of the title compound and two molecules of 2-propanol as the building unit according to analysis of the distribution of pairwise interaction energies. A molecular docking study was carried out to evaluate the interactions of the title compound with the active centers of macromolecules corresponding to viral targets, namely, anti-hepatitis B activity [HBV, capsid Y132A mutant (VCID 8772) PDB ID: 5E0I] and anti-COVID-19 main protease activity (PDB ID: 6LU7). The data obtained revealed a noticeable affinity towards them that exceeded that of the reference ligands.

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“…It is also worth mentioning that our previous experience in quinolones chemistry [23][24][25] gave a powerful background for the planning stage of this research.…”

Section: Introductionmentioning

confidence: 99%

The Search for New Antibacterial Agents among 1,2,3-Triazole Functionalized Ciprofloxacin and Norfloxacin Hybrids: Synthesis, Docking Studies, and Biological Activity Evaluation

et al. 2021

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Among all modern antibiotics, fluoroquinolones are well known for their broad spectrums of activity and efficiency toward microorganisms and viruses. However, antibiotic resistance is still a problem, which has encouraged medicinal chemists to modify the initial structures in order to combat resistant strains. Our current work is aimed at synthesizing novel hybrid derivatives of ciprofloxacin and norfloxacin and applying docking studies and biological activity evaluations in order to find active promising molecules. We succeeded in the development of a synthetic method towards 1,2,3-triazole-substituted ciprofloxacin and norfloxacin derivatives. The structure and purity of the obtained compounds were confirmed by 1H NMR, 13C NMR, 19F NMR, LC/MS, UV-, IR- spectroscopy. Docking studies, together with in vitro research against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633, Pseudomonas aeruginosa ATCC 27853, Candida albicans NCTC 885-653 revealed compounds in which activity exceeded the initial molecules.

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Alkylation of 3‐Phenyl‐1H‐pyrazolo[4,3‐c] quinoline: Theoretical Analysis of Regioselectivity

Cited by 11 publications

References 9 publications

Structural modification of ciprofloxacin and norfloxacin for searching new antibiotics to combat drug-resistant bacteria

Structural modification of ciprofloxacin and norfloxacin for searching new antibiotics to combat drug-resistant bacteria

Synthesis, analysis of molecular and crystal structures, estimation of intermolecular interactions and biological properties of 1-benzyl-6-fluoro-3-[5-(4-methylcyclohexyl)-1,2,4-oxadiazol-3-yl]-7-(piperidin-1-yl)quinolin-4-one

The Search for New Antibacterial Agents among 1,2,3-Triazole Functionalized Ciprofloxacin and Norfloxacin Hybrids: Synthesis, Docking Studies, and Biological Activity Evaluation

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