Search

Your search keyword '"Nikolay U. Zyk"' showing total 3 results
Start Over Author "Nikolay U. Zyk"
3 results on '"Nikolay U. Zyk"'

1. Synthesis and Preclinical Evaluation of Small-Molecule Prostate-Specific Membrane Antigen-Targeted Abiraterone Conjugate

Author

Aleksei E. Machulkin, Ekaterina A. Nimenko, Nikolay U. Zyk, Anastasiia A. Uspenskaia, Galina B. Smirnova, Irina I. Khan, Vadim S. Pokrovsky, Alexander N. Vaneev, Roman V. Timoshenko, Vugara V. Mamed-Nabizade, Maria V. Zavertkina, Alexander Erofeev, Petr Gorelkin, Alexander G. Majouga, Nikolay V. Zyk, Elena S. Khazanova, and Elena K. Beloglazkina

Subjects
prostate cancer, abiraterone, drug delivery, prostate-specific membrane antigen, Organic chemistry, QD241-441
Abstract

Prostate cancer is the second most common type of cancer among men. The main method of its treatment is androgen deprivation therapy, which has a wide range of side effects. One of the solutions to this challenge is the targeted delivery of drugs to prostate cancer cells. In this study, we performed the synthesis of a novel small-molecule PSMA-targeted conjugate based on abiraterone. Cytotoxicity, the induction of intracellular reactive oxygen species, and P450-cytochrome species inhibition were investigated for this conjugate PSMA-abiraterone. The conjugate demonstrated a preferential effect on prostate tumor cells, remaining inactive at up to 100 µM in human fibroblast cells. In addition, it revealed preferential efficacy, specifically on PSMA-expressing lines with a 65% tumor growth inhibition level on 22Rv1 (PSMA+) xenografts after 14-fold oral administration of PSMA-Abi at a single dose of 500 mg/kg (7.0 g/kg total dose) was observed. This compound showed significantly reduced acute toxicity with comparable efficacy compared to AbiAc.

Published
2022
Full Text
View/download PDF

2. Synthesis and Biological Evaluation of PSMA Ligands with Aromatic Residues and Fluorescent Conjugates Based on Them

Author

Nikolay V. Zyk, Irina V. Saltykova, Anastasiya V Aladinskaya, Alexander Erofeev, Olga O. Krasnovskaya, Radik R. Shafikov, Elena K. Beloglazkina, Anastasiia S Garanina, Oleg Yu. Saveliev, Maxim A. Abakumov, Vladimir I. Polshakov, Ekaterina A. Nimenko, Yan A. Ivanenkov, Aleksei E. Machulkin, Olga A. Dontsova, Emil U Yamansarov, Alexander G. Majouga, Elena S. Khazanova, Anastasia A. Uspenskaya, Anton P. Ber, Galina B. Smirnova, Vadim S. Pokrovsky, Nikolay U. Zyk, Dmitry A. Skvortsov, Petr V. Gorelkin, Stanislav A. Petrov, A. V. Finko, and Rauf T Akhmirov

Subjects
Glutamate Carboxypeptidase II, Male, Cell Survival, Transplantation, Heterologous, Mice, Nude, Antineoplastic Agents, urologic and male genital diseases, Ligands, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Mice, Structure-Activity Relationship, Cell Line, Tumor, Drug Discovery, Glutamate carboxypeptidase II, Aromatic amino acids, Structure–activity relationship, Animals, Humans, Tissue Distribution, 030304 developmental biology, Fluorescent Dyes, 0303 health sciences, Ligand, Chemistry, Optical Imaging, Prostatic Neoplasms, In vitro, 0104 chemical sciences, Transplantation, 010404 medicinal & biomolecular chemistry, Biochemistry, Antigens, Surface, Molecular Medicine, Drug Screening Assays, Antitumor, Linker, Conjugate
Abstract

Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII), is a suitable target for specific delivery of antitumor drugs and diagnostic agents due to its overexpression in prostate cancer cells. In the current work, we describe the design, synthesis, and biological evaluation of novel low-molecular PSMA ligands and conjugates with fluorescent dyes FAM-5, SulfoCy5, and SulfoCy7. In vitro evaluation of synthesized PSMA ligands on the activity of PSMA shows that the addition of aromatic amino acids into a linker structure leads to a significant increase in inhibition. The conjugates of the most potent ligand with FAM-5 as well as SulfoCy5 demonstrated high affinities to PSMA-expressing tumor cells in vitro. In vivo biodistribution in 22Rv1 xenografts in Balb/c nude mice of PSMA-SulfoCy5 and PSMA-SulfoCy7 conjugates with a novel PSMA ligand demonstrated good visualization of PSMA-expressing tumors. Also, the conjugate PSMA-SulfoCy7 demonstrated the absence of any explicit toxicity up to 87.9 mg/kg.

Published
2021

3. Synthesis and biological evaluation of PSMA-targeting paclitaxel conjugates

Author

E. A. Plotnikova, Raisa I. Yakubovskaya, Nikolay U. Zyk, Yan A. Ivanenkov, Mikhail V. Kavalchuk, Elena K. Beloglazkina, Anastasia V. Aladinskaya, Alexander G. Majouga, Victor Koteliansky, Alexey E. Machulkin, Ekaterina A. Nimenko, Dmitry A. Skvortsov, Nikolay V. Zyk, Anton P. Ber, Radik R. Shafikov, and Anastasia A. Uspenskaya

Subjects
Male, Paclitaxel, Clinical Biochemistry, Pharmaceutical Science, 01 natural sciences, Biochemistry, Prostate cancer, chemistry.chemical_compound, Mice, Drug Delivery Systems, Prostate, Drug Discovery, LNCaP, medicine, Glutamate carboxypeptidase II, Animals, Humans, Cytotoxicity, Molecular Biology, 010405 organic chemistry, Chemistry, Organic Chemistry, Prostatic Neoplasms, medicine.disease, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, medicine.anatomical_structure, Targeted drug delivery, Drug delivery, Cancer research, Molecular Medicine
Abstract

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.

Published
2019

Catalog

Books, media, physical & digital resources
See catalog results