EVALUATION OF CEPHALOSPORIN’S LIPOPHILIC PROPERTIES

  • Natalia N. Kataeva Ural State Medical University
  • Natalia A. Naronova Ural State Medical University
  • Kristina O. Golitsyna Ural State Medical University
  • Nadezda A. Belokonova Ural State Medical University
  • Ksenia E. Shulepova Ural State Medical University
Keywords: lipophilicity, antibiotics, cephalosporins, osmometry, partition coefficient in the «oil/water» system

Abstract

As a part of the study, a comparative analysis of different generations three representative’s lipophilic properties of cephalosporin antibiotics, namely cefazolin, cefotaxime and cefepime, was carried out. Lipophilicity is a very important physicochemical property of medicinal substances, since it determines their ability to pass through protective barriers, distribute, accumulate in tissues and body fluids, be broken down and excreted, which, in turn, affects the manifestation of antibacterial activity and the cytotoxic effect of antibiotics. During the experiment, a series of drugs aqueous solutions were prepared, then the antibiotics were extracted with highly purified olive oil, after which the aqueous phase was taken and the osmolality value for it was determined. Based on the calibration dependences of the osmolality value on the concentration of the antibiotic in the aqueous phase after extraction, the logarithms of the distribution coefficients in the «oil/water» system were calculated, which is a numerical indicator of the lipophilicity of substances. Using the capabilities of the online platform «Molinspiration Cheminformatics Software», the theoretical values of the studied drugs distribution coefficients logarithms were also determined, and the theoretical values correlated with the experimental ones. Based on the data obtained, it was revealed that the studied antibiotics have low lipophilicity, which decreases in the order: cefotaxime > cefazolin > cefepime. The work also assessed the relationship between solution pH and lipophilic properties. Pearson's r-coefficients between pH and antibiotic concentrations in oil after extraction of cefotaxime and cefazolin show a weak inverse relationship between the studied parameters. For cefepime solutions, a similar linear correlation coefficient demonstrates a direct high relationship between the pH of the solution and the lipophilicity of the antibiotic. The results of the study can be taken into account during antibiotic therapy with appropriate cephalosporins, as well as when creating a new generation of antibiotics.

For citation:

Kataeva N.N., Naronova N.A., Golitsyna K.O., Belokonova N.A., Shulepova K.E. Evaluation of cephalosporin’s lipophilic properties. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2024. V. 67. N 7. P. 55-62. DOI: 10.6060/ivkkt.20246707.7018.

References

Zyryanov S.K., Butranova O.I. Modern approaches to the rational choice of antibiotics for the treatment of community-acquired pneumonia in various categories of patients. Kach. Klin. Praktika. 2019. N 1. P. 97-113 (in Russian).

Omarova S.M., Bagandova D.SH., Saidova P.S. Study of antibiotic sensitivity of opportunistic microbiota isolated from women with mixed chlamodial infection. Ur. Med. Zhurn. 2020. V. 194. N 11. P. 112-116 (in Russian). DOI: 10.25694/URMJ.2020.11.29.

Omarova S.M., Isaeva R.I., Saidova P.S., Akaeva F.S., Bagandova D.S. Analysis of the etiological structure and antibiotic sensitivity of patents to infection of respiratory tract determined in Makhachkala. Ur. Med. Zhurn. 2019. N 3. P. 101-103 (in Russian). DOI: 10.25694/URMJ.2019.03.31.

Kurbanova D.I., Kosimkhozhiev M.I. Clinical experience with the fifth-generation cephalosporin Zinforo. Ekonomika Sotsium. 2023. V. 6. N 2. P. 820-823 (in Russian).

Shah S., Barton G., Fischer A. Pharmacokinetic considerations and dosing strategies of antibiotics in the criticallyill patient. J. Intens. Care Soc. 2015. V. 16. N 2. P. 147-153. DOI: 10.1177/1751143714564816.

Postnikov S.S. The toxic effects of antibiotics. Pediatriya. Zhurn. im. G.N. Speranskogo. 2008. 87 (2). P. 21 (in Russian).

Hughes J.D. Physiochemical drug properties associated with in vivo toxicological outcomes. Bioorg. Med. Chem. Lett. 2008. V. 18. N 17. P. 4872-4875. DOI: 10.1016/j.bmcl.2008.07.071.

Hodges G. A comparison of log Kow (n-octanol–water par-tition coefficient) values for non-ionic, anionic, cationic and amphoteric surfactants determined using predictions and ex-perimental methods. Env. Sci. Eur. 2019. V. 31. N 1. P. 1-18. DOI: 10.1186/s12302-018-0176-7.

Leo A., Hansch C., Elkins D. Partition coefficients and their uses. Chem. Rev. 1971. V. 71. N 6. Р. 525-616. DOI: 10.1021/cr60274a001.

Lutfullina G.G., Fatkhutdinova A.A. Synthesis and study of the properties of a nonionogenic surfactant based on fatty acids of corn oil and diethanolamine. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2022. V. 65. N 11. P. 20-26 (in Russian). DOI: 10.6060/ivkkt.20226511.6640.

Brown P. Influence of lipophilicity on the antibacterial activity of polymyxin derivatives and on their ability to act as potentiators of rifampicin. ACS Infect. Dis. 2021. V. 7. N 4. P. 894-905. DOI: 10.1021/acsinfecdis.0c00917.

Kolarič A. A Fine-Tuned Lipophilicity/Hydrophilicity Ratio Governs Antibacterial Potency and Selectivity of Bifurcated Halogen Bond-Forming NBTIs. Antibiotics. 2021. V. 10. N 7. P. 862. DOI: 10.3390/antibiotics10070862.

Ivantsova N.L. Minocycline: clinical and farmacological aspects of antibiotic therapy in patients with acne. Krym. Terap. Zhurn. 2022. N 4. P. 42-45 (in Russian).

Petrovskii F.I., Knyazheskaya N.P. Budesonide in the treatment of allergic respiratory diseases. Prakt. Pul'monologiya. 2007. N 2. P. 43-46 (in Russian).

Olina A.A., Karpunina T.I., Mashurov M.G. The peculiarities of pharmacokinetic characteristics of antifungal drugs and efficacy of therapy of vulvovaginal candidosis. Ur. Med. Zhurn. 2009. V. 57. N 3. P. 54-58 (in Russian).

Kozina O.E., Vikulova M.A. Sorptive interaction of potas-sium polititanate with cobalt(II) ions. Mezhdunar. Nauch.-Issl. Zhurn. 2022. V. 11. N 125. P. 6 (in Russian). DOI: 10.23670/IRJ.2022.125.85.

Aslamova V.S., Shalunts L.V., Aslamov A.A., Grabel'nykh V.A. Computer simulationof the sorption of heavy metal ions by a sulphur-containing modified zeolite. Izv. Vuzov. Prikl. Khim. Biotekhnol. 2020. V. 10. N 4. P. 564–572 (in Russian). DOI: 10.21285/2227-2925-2020-10-4-564-572.

Evdokimova E.V., Panova T.M., Yur'ev Yu.L. Features of the structure and properties of active coals obtained fromaspen. Derevoobr. Promst'. 2020. N 2. P. 87-92 (in Russian).

Chuckova N.N., Soloviev A.A., Kanunnikova O.M. The influence of mechanical activation of creatine and creatinine on the electrokinetic activity of buccal epithelial cells and erythrocytes. Ur. Med. Zhurn. 2018. N 12 (167). P. 159-164 (in Russian). DOI: 10.25694/URMJ.2018.12.18.

Finean J. Biologicheskieul'trastruktury. M.: Mir. 1970. 325 p. (in Russian).

Rendal C., Kusk K.O., Trapp S. Optimal choice of pH for toxicity and bioaccumulation studies of ionizing organic chemicals. Env. Toxicol. Chem. 2011. V. 30. N 11. P. 2395-2406. DOI: 10.1002/etc.641.

Salasina Ya.Yu., Deineka V.I., Blinova I.P., Oleynits E.Yu., Deineka L.A., Makarevich S.L. Control of the se-lectivity of the separation of grape Anthocyanidin 3-glucosides and 3,5-diglucosides: determination of anthocyanins in grape fruit grown in the Belgorod region. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2023. V. 66. N 5. P. 72-79 (in Russian). DOI: 10.6060/ivkkt.20236605.6784.

Published
2024-05-30
How to Cite
Kataeva, N. N., Naronova, N. A., Golitsyna, K. O., Belokonova, N. A., & Shulepova, K. E. (2024). EVALUATION OF CEPHALOSPORIN’S LIPOPHILIC PROPERTIES. ChemChemTech, 67(7), 55-62. https://doi.org/10.6060/ivkkt.20246707.7018
Section
CHEMISTRY (inorganic, organic, analytical, physical, colloid and high-molecular compounds)