Bioorganic and Medicinal Chemistry Letters, volume 29, issue 10, pages 1246-1255
Synthesis and biological evaluation of Doxorubicin-containing conjugate targeting PSMA
Ivanenkov Yan
1
,
Beloglazkina Elena K
,
Uspenskaya Anastasia A
,
Skvortsov Dmitry A.
,
Garanina Anastasia S
,
Zyk Nikolay V.
2
,
Vorobyeva Nataliya S
3
,
Machulkin Alexey E.
2
,
Deyneka Ekaterina V.
4
,
Trofimenko Alexander V.
4
,
Koteliansky Victor E.
2
,
Bezrukov Dmitry S.
,
Puchinina Maria M.
4
,
Riabykh Grigory K
2
,
Sofronova Alina A.
5
,
Malyshev Alexander S.
6
,
Garanina A. S.
7, 8
,
Skvortsov Dmitry
2
,
Bezrukov Dmitry S.
8, 9
,
Aladinskaya Anastasia V.
4
3
Centaura LLC, Moscow, Russia.
|
Publication type: Journal Article
Publication date: 2019-05-01
Quartile SCImago
Q2
Quartile WOS
Q2
Impact factor: 2.7
ISSN: 0960894X, 14643405
Organic Chemistry
Drug Discovery
Biochemistry
Molecular Biology
Pharmaceutical Science
Clinical Biochemistry
Molecular Medicine
Abstract
Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII), has recently emerged as a prominent biomarker of prostate cancer (PC) and as an attractive protein trap for drug targeting. At the present time, several drugs and molecular diagnostic tools conjugated with selective PSMA ligands are actively evaluated in different preclinical and clinical trials. In the current work, we discuss design, synthesis and a preliminary biological evaluation of PSMA-specific small-molecule carrier equipped by Doxorubicin (Dox). We have introduced an unstable azo-linker between Dox and the carrier hence the designed compound does release the active substance inside cancer cells thereby providing a relatively high Dox concentration in nuclei and a relevant cytotoxic effect. In contrast, we have also synthesized a similar conjugate with a stable amide linker and it did not release the drug at all. This compound was predominantly accumulated in cytoplasm and did not cause cell death. Preliminary in vivo evaluation has showed good efficiency for the degradable conjugate against PC3-PIP(PSMA+)-containing xenograft mine. Thus, we have demonstrated that the conjugate can be used as a template to design novel analogues with improved targeting, anticancer activity and lower rate of potential side effects. 3D molecular docking study has also been performed to elucidate the underlying mechanism of binding and to further optimization of the linker area for improving the target affinity.
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- We do not take into account publications that without a DOI.
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- Statistics recalculated weekly.
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Ivanenkov Y. et al. Synthesis and biological evaluation of Doxorubicin-containing conjugate targeting PSMA // Bioorganic and Medicinal Chemistry Letters. 2019. Vol. 29. No. 10. pp. 1246-1255.
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Machulkin A. E., Majouga A. G., Malyshev A. S., Sofronova A. A., Riabykh G. K., Puchinina M. M., Vorobyeva N. S., V. Aladinskaya A., Bezrukov D. S., Koteliansky V. E., Zyk N. V., Beloglazkina E. K., Trofimenko A. V., Deyneka E. V., Uspenskaya A. A., Skvortsov D. A., Garanina A. S., Ivanenkov Y., Garanina A. S., Skvortsov D., Uspenskaya A. A., Beloglazkina E. K., Bezrukov D. S., Aladinskaya A. V. Synthesis and biological evaluation of Doxorubicin-containing conjugate targeting PSMA // Bioorganic and Medicinal Chemistry Letters. 2019. Vol. 29. No. 10. pp. 1246-1255.
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TY - JOUR
DO - 10.1016/j.bmcl.2019.01.040
UR - https://doi.org/10.1016%2Fj.bmcl.2019.01.040
TI - Synthesis and biological evaluation of Doxorubicin-containing conjugate targeting PSMA
T2 - Bioorganic and Medicinal Chemistry Letters
AU - Ivanenkov, Yan
AU - Machulkin, Alexey E.
AU - Garanina, Anastasia S
AU - Skvortsov, Dmitry A.
AU - Uspenskaya, Anastasia A
AU - Deyneka, Ekaterina V.
AU - Trofimenko, Alexander V.
AU - Beloglazkina, Elena K
AU - Zyk, Nikolay V.
AU - Koteliansky, Victor E.
AU - Bezrukov, Dmitry S.
AU - V. Aladinskaya, Anastasia
AU - Vorobyeva, Nataliya S
AU - Puchinina, Maria M.
AU - Riabykh, Grigory K
AU - Sofronova, Alina A.
AU - Malyshev, Alexander S.
AU - Majouga, Alexander G.
AU - Garanina, A. S.
AU - Skvortsov, Dmitry
AU - Uspenskaya, Anastasia A.
AU - Beloglazkina, Elena K.
AU - Bezrukov, Dmitry S.
AU - Aladinskaya, Anastasia V.
PY - 2019
DA - 2019/05/01 00:00:00
PB - Elsevier
SP - 1246-1255
IS - 10
VL - 29
SN - 0960-894X
SN - 1464-3405
ER -
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@article{2019_Ivanenkov,
author = {Yan Ivanenkov and Alexey E. Machulkin and Anastasia S Garanina and Dmitry A. Skvortsov and Anastasia A Uspenskaya and Ekaterina V. Deyneka and Alexander V. Trofimenko and Elena K Beloglazkina and Nikolay V. Zyk and Victor E. Koteliansky and Dmitry S. Bezrukov and Anastasia V. Aladinskaya and Nataliya S Vorobyeva and Maria M. Puchinina and Grigory K Riabykh and Alina A. Sofronova and Alexander S. Malyshev and Alexander G. Majouga and A. S. Garanina and Dmitry Skvortsov and Anastasia A. Uspenskaya and Elena K. Beloglazkina and Dmitry S. Bezrukov and Anastasia V. Aladinskaya},
title = {Synthesis and biological evaluation of Doxorubicin-containing conjugate targeting PSMA},
journal = {Bioorganic and Medicinal Chemistry Letters},
year = {2019},
volume = {29},
publisher = {Elsevier},
month = {may},
url = {https://doi.org/10.1016%2Fj.bmcl.2019.01.040},
number = {10},
pages = {1246--1255},
doi = {10.1016/j.bmcl.2019.01.040}
}
Cite this
MLA
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Ivanenkov, Yan, et al. āSynthesis and biological evaluation of Doxorubicin-containing conjugate targeting PSMA.ā Bioorganic and Medicinal Chemistry Letters, vol. 29, no. 10, May. 2019, pp. 1246-1255. https://doi.org/10.1016%2Fj.bmcl.2019.01.040.