Synthesis and biological evaluation of PSMA-targeting paclitaxel conjugates.

Animals Drug Delivery Systems / methods Humans Male Mice Paclitaxel / chemical synthesis Prostatic Neoplasms / drug therapy
Drug delivery Paclitaxel Prostate cancer Prostate-specific membrane antigen

Journal

Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377

Informations de publication

Date de publication:
15 08 2019
Historique:
received: 08 05 2019
revised: 17 06 2019
accepted: 19 06 2019
pubmed: 30 6 2019
medline: 18 9 2020
entrez: 29 6 2019
Statut: ppublish

Résumé

Prostate cancer (PC) is the second most commonly occurring cancer in men. Conventional chemotherapy has wide variety of disadvantages such as high systemic toxicity and low selectivity. Targeted drug delivery is a promising approach to decrease side effects of therapy. Prostate specific membrane antigen (PSMA) is overexpressed in prostate cancer cells while low level of expression is observed in normal cells. In this study we describe the development of Glu-urea-Lys based PSMA-targeting conjugates with paclitaxel. A series of new PSMA targeting conjugates with paclitaxel was designed and synthesized. The cytotoxicity of conjugates was evaluated against prostate (LNCaP, 22Rv1 and PC-3) and non-prostate (Hek293T, VA13, A549 and MCF-7) cell lines. The most promising conjugate 21 was examined in vivo using 22Rv1 xenograft mice model. It demonstrated good efficiency comparable with paclitaxel, while reduced toxicity. 3D molecular docking study was also performed to understand underlying mechanism of binding and further optimization of the linker substructure and conjugates structure for improving the target affinity. These conjugates may be useful for further design of novel PSMA targeting delivery systems for PC.

Identifiants

DOI: 10.1016/j.bmcl.2019.06.035 PMID: 31248772
pubmed: 31248772
pii: S0960-894X(19)30412-3
doi: 10.1016/j.bmcl.2019.06.035
pii:
doi:

Substances chimiques

Paclitaxel P88XT4IS4D

Types de publication

Letter Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2229-2235

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

Auteurs

Alexey E Machulkin (AE)

Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation; Institute of Biochemistry and Genetics Ufa Science Centre Russian Academy of Sciences (IBG RAS), Oktyabrya Prospekt 71, 450054 Ufa, Russian Federation. Electronic address: alekseymachulkin@rambler.ru.

Dmitry A Skvortsov (DA)

Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation. Electronic address: skvorratd@mail.ru.

Yan A Ivanenkov (YA)

Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation; Moscow Institute of Physics and Technology (State University), 9 Institutskiy lane, Dolgoprudny City, Moscow Region 141700, Russian Federation; National University of Science and Technology MISiS, 9 Leninskiy pr, Moscow 119049, Russian Federation; ChemDiv, San Diego, CA, USA; Institute of Biochemistry and Genetics Ufa Science Centre Russian Academy of Sciences (IBG RAS), Oktyabrya Prospekt 71, 450054 Ufa, Russian Federation.

Anton P Ber (AP)

Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation.

Mikhail V Kavalchuk (MV)

Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation.

Anastasia V Aladinskaya (AV)

Moscow Institute of Physics and Technology (State University), 9 Institutskiy lane, Dolgoprudny City, Moscow Region 141700, Russian Federation.

Anastasia A Uspenskaya (AA)

Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation.

Radik R Shafikov (RR)

Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation.

Ekaterina A Plotnikova (EA)

P. A. Herzen Moscow Oncology Research Institute, 3, 2th Botkinsky Driveway, Moscow 125284, Russian Federation.

Raisa I Yakubovskaya (RI)

P. A. Herzen Moscow Oncology Research Institute, 3, 2th Botkinsky Driveway, Moscow 125284, Russian Federation.

Ekaterina A Nimenko (EA)

Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation.

Nikolay U Zyk (NU)

Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation.

Elena K Beloglazkina (EK)

Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation.

Nikolay V Zyk (NV)

Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation.

Victor E Koteliansky (VE)

Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation.

Alexander G Majouga (AG)

Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation; National University of Science and Technology MISiS, 9 Leninskiy pr, Moscow 119049, Russian Federation; Dmitry Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, Moscow 125047, Russian Federation.

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Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › Synthesis and biological evaluation of...
Recherchemedicale.com › Thérapeutique › Traitement médicamenteux › Systèmes de délivrance de médicaments › Synthesis and biological evaluation of...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Synthesis and biological evaluation of...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Synthesis and biological evaluation of...
Recherchemedicale.com › Composés chimiques organiques › Hydrocarbures › Terpènes › Diterpènes › Taxoïdes › Paclitaxel › Synthesis and biological evaluation of...
Recherchemedicale.com › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › Synthesis and biological evaluation of...