Synthesis and initial in vitro evaluation of PSMA-targeting ligands with a modified aromatic moiety at the lysine ε-nitrogen atom

Nikolai Y Zyk; Anton P Ber; Ekaterina A Nimenko; Radik R Shafikov; Sergei A Evteev; Stanislav A Petrov; Anastasia A Uspenskaya; Natalia S Dashkova; Yan A Ivanenkov; Dmitry A Skvortsov; Elena K Beloglazkina; Alexander G Majouga; Aleksei E Machulkin

doi:10.1016/j.bmcl.2022.128840

Synthesis and initial in vitro evaluation of PSMA-targeting ligands with a modified aromatic moiety at the lysine ε-nitrogen atom

Bioorg Med Chem Lett. 2022 Sep 1:71:128840. doi: 10.1016/j.bmcl.2022.128840. Epub 2022 May 31.

Affiliations

¹ Lomonosov Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation. Electronic address: Zyknikola@gmail.com.
² Lomonosov Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation.
³ Lomonosov Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences, GSP-7, Ulitsa Miklukho-Maklaya, 16/10, Moscow 117997, Russian Federation.
⁴ The Federal State Unitary Enterprise Dukhov Automatics Research Institute, Moscow, 127055, Russia.
⁵ Lomonosov Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation; The Federal State Unitary Enterprise Dukhov Automatics Research Institute, Moscow, 127055, Russia.
⁶ Lomonosov Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation; Dmitry Mendeleev University of Chemical Technology of Russia, Miusskaya Sq. 9, Moscow 125047, Russian Federation.
⁷ Lomonosov Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation; RUDN University, Miklukho-Maklaya Str. 6, Moscow 117198, Russian Federation.

PMID: 35661685
DOI: 10.1016/j.bmcl.2022.128840

Abstract

We report an improved series of ligands targeting prostate specific membrane antigen (PSMA). The new compounds were designed by the introduction of changes in the structure of the aromatic fragment at ε-nitrogen atom of lysine that resulted in improved biological parameters. Some of them demonstrated high selectivity and nanomolar IC₅₀ values. We synthesized and tested two conjugates with a fluorescent label Sulfo-Cy5 as an example of the use of the obtained PSMA inhibitors as a basis for the creation of diagnostic preparations.

Keywords: Drug delivery; Ligands; Prostate cancer; Prostate-specific membrane antigen; Sulfo-Cy5.

Publication types

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

MeSH terms

Antigens, Surface
Cell Line, Tumor
Glutamate Carboxypeptidase II
Humans
Ligands
Lysine*
Male
Nitrogen
Prostatic Neoplasms*

Substances

Antigens, Surface
Ligands
Glutamate Carboxypeptidase II
Lysine
Nitrogen