Synthesis and inhibitory activity of atorvastatin conjugate with a branched asialoglycoprotein receptor ligand with 3 N-acetyl-d-galactosamine residues

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

The novel atorvastatin conjugate was synthesized in a multi-step procedure using branched N -acetylgalactosamine ligand for asialoglycoprotein receptor targeting. The molar solubility of the obtained conjugate was 6.1±0.9 mM, which is almost 60 times higher than that of unmodified atorvastatin. The hydrolysis products of the conjugate demonstrated effective inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase.

About the authors

S. Yu. Maklakova

Lomonosov Moscow State University

Email: maklakovasu@yandex.ru

M. P Mazhuga

Lomonosov Moscow State University

Email: maklakovasu@yandex.ru

A. V Lopukhov

Lomonosov Moscow State University

Email: maklakovasu@yandex.ru

K. R Gibadullina

Lomonosov Moscow State University

Email: maklakovasu@yandex.ru

N. L Klyachko

Lomonosov Moscow State University

Email: maklakovasu@yandex.ru

A. G Majouga

Lomonosov Moscow State University;Dmitry Mendeleev University of Chemical Technology of Russia

Email: maklakovasu@yandex.ru

E. K Beloglazkina

Lomonosov Moscow State University

Email: maklakovasu@yandex.ru

References

  1. Рациональная фармакотерапия сердечно-сосудистых заболеваний. Ред. Е.И. Чазов, Ю.А. Карпов. М.: Литтерра. 2016.
  2. Vardanyan R., Hruby V. Synthesis of Best-seller Drugs. London-San Diego-Cambridge-Oxford: Academic Press. 2016, 286-293.
  3. Bratton L.D., Auerbach B., Choi C., Dillon L., Hanselman J.C., Larsen S.D., Lu G., Olsen K., Pfefferkorn J.A., Robertson A., Sekerke C., Trivedi B.K., Unangst P.C. Bioorg. Med. Chem. 2007, 15, 5576-5589. doi: 10.1016/j.bmc.2007.05.031
  4. Rageh A.H., Atia N.N., Abdel-Rahman H.M. J. Pharm. Biomed. Anal. 2017, 142, 7-14. doi: 10.1016/j.jpba.2017.04.037
  5. Roth B.D., Bocan T.M.A., Blankley C.J., Chucholowski A.W., Creger P.L., Creswell M.W., Ferguson E., Newton R.S., O'Brien P. J. Med. Chem. 1991, 34, 463-466. doi: 10.1021/jm00105a071
  6. Zhang Y., Zhang X., Zeng C., Li B., Zhang C., Li W., Hou X., Dong Y. Bioorg. Med. Chem. 2019, 27, 2187-2191. doi: 10.1016/j.bmc.2019.04.019
  7. D'Souza A.A., Devarajan P.V. J. Control. Rel. 2015, 203, 126-139. doi: 10.1016/j.jconrel.2015.02.022
  8. Wang Q., Huang C., Jiang M., Zhu Y., Wang J., Chen J., Shi J. Spectrochim. Acta A: Mol. Biomol. Spectroscopy. 2016, 156, 155-163. doi: 10.1016/j.saa.2015.12.003
  9. Galiullina L.F., Scheidt H.A., Huster D., Aganov A., Klochkov V. Biochim. Biophys. Acta - Biomembr. 2019, 1861, 584-593. doi: 10.1016/j.bbamem.2018.12.013
  10. Huang X., Leroux J.-C., Castanger B. Bioconjugate Chem. 2017, 28, 283-295. doi: 10.1021/acs.bioconjchem.6b00651
  11. Cardona C.M., Gawley R.E. J. Org. Chem. 2002, 67, 1411-1413. doi: 10.1021/jo0161678
  12. Manoharan M., Rajeev K., Nair J., Maier M. Европ. заявка EP 3156077. 2022.
  13. Vickers S., Duncan C.A., Chen I.W., Rosegay A., Duggan D.E. Drug Metab. Dispos. 1990, 18, 138-145.
  14. Vickers S., Duncan C.A., Vyas K.P., Kari P.H., Arison B., Prakash S.R., Ramjit H.G., Pitzenberger S.M., Stokker G., Duggan D.E. Drug Metab. Dispos. 1990, 18, 476-483.
  15. Petrov R.A., Mefedova S.R., Yamansarov E.Y., Maklakova S.Y., Grishin D.A., Lopatukhina E.V., Burenina O.Y., Lopukhov A.V., Kovalev S.V., Timchenko R.V., Ondar E.E., Ivanenkov Y.A., Evteev S.A., Vaneev A.N., Timoshenko R.V., Klyachko N.L., Erofeev A.S., Gorelkin P.V., Beloglazkina E.K., Majouga A.G. Mol. Pharmaceutics. 2021, 18, 461-468. doi: 10.1021/acs.molpharmaceut.0c00980
  16. Mizoi K., Takahashi M., Haba M., Hosokawa M. Bioorg. Med. Chem. Lett. 2016, 26, 921-923. doi: 10.1016/j.bmcl.2015.12.069

Copyright (c) 2023 Russian Academy of Sciences

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies