Anti-tumor and anti-metastatic properties of bromo- and bis(2-chloroethyl)amino-substituted derivatives of N-methyl ethyl esters of indole-3-carboxylic acid in the S-37 sarcoma mouse model
O. V. Soldatova,
M. V. Filimonova,
V. I. Surinova,
A. A. Shitova,
V. A. Rybachuk,
K. A. Nikolaev,
A. O. Kosachenko,
E. A. Prosovskaya,
G. A. Demyashkin,
P. V. Shegai,
S. A. Ivanov,
A. D. Kaprin,
A. S. Filimonov https://doi.org/10.37748/2686-9039-2026-7-1-1
EDN: DCMGEC
Abstract
The Laboratory of Radiation Pharmacology has previously developed water-soluble dialkylaminoalkyl esters of indole‑3‑carboxylic acid, which demonstrated high immunomodulatory, antiviral, and antitumor activity. Based on these established properties, we aimed to enhance their antitumor effect by incorporating cytotoxic alkylating bromo- or bis(2‑chloroethyl)amino substituents into their molecular structure. Compounds T1167 and T1089 were successfully synthesized.
Purpose of the study. To investigate the antitumor and antimetastatic properties of bromo-, bis(2‑chloroethyl)amino-substituted derivatives of N-methyl ethyl esters of indole‑3‑carboxylic acid (T1089 and T1167).
Materials and methods. The study was performed on 65 mice with subcutaneously transplanted lymphogenously metastasizing sarcoma S‑37 (9 × 105 cells/mouse). Compounds were administered intraperitoneally: T1089 at 40 mg/kg, T1167 at 30 mg/kg. Antitumor efficacy was assessed by primary tumor growth dynamics, morphometric and histological parameters.
Results. The studied compounds inhibited primary tumor growth of sarcoma S‑37 (TGI for T1089–22,4 %, for T1167–30,5 %), increased dystrophic and necrotic changes in tumors (T1089 – by 36 %, T1167 – by 55 %), reduced mitotic index by 2‑fold, and exhibited antimetastatic activity, decreasing metastatic areas in inguinal lymph nodes (day 10: T1089 – by 76 %, T1167 – by 89 %) and iliac lymph nodes (day 10: T1089 – by 28,7 %, T1167 – by 60,8 %; day 16: T1089 – by 53,3 %, T1167 – by 45,6 %).
Conclusion. Antitumor and antimetastatic activity of compounds T1089 and T1167 was demonstrated in the sarcoma S‑37 model. The obtained data indicate the promise of compounds combining alkylating cytotoxicity with the immunomodulatory potential inherent to this class. Further research will involve preclinical development including safety assessment, expansion of the range of tumor models studied, and detailed investigation of the mechanisms of action.
About the Authors
O. V. Soldatova
https://new.nmicr.ru/mrrc/
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
Obninsk, Russian Federation
Olga V. Soldatova – Junior Researcher, Laboratory of Radiation Pharmacology, A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Obninsk, Russian Federation ORCID: https://orcid.org/0000-0002-1178-3560, eLibrary SPIN: 5027-7324, Author ID: 1066587, Scopus Author ID: 57220804924, WoS ResearcherID: ABC-5730-2020
Competing Interests:
Sergey A. Ivanov, Andrey D. Kaprin is the member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
M. V. Filimonova
https://new.nmicr.ru/mrrc/
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
Obninsk, Russian Federation
Marina V. Filimonova – Dr. Sci. (Biology), Head of the Laboratory of Radiation Pharmacology, A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Obninsk, Russian Federation ORCID: https://orcid.org/0000-0002-9690-4746, eLibrary SPIN: 3344-9998, Author ID: 638642, Scopus Author ID: 36894092800, WoS ResearcherID: AAQ-9017-2020
Competing Interests:
Sergey A. Ivanov, Andrey D. Kaprin is the member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
V. I. Surinova
https://new.nmicr.ru/mrrc/
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
Obninsk, Russian Federation
Valentina I. Surinova – Cand. Sci. (Chemistry), Senior Researcher, Laboratory of Radiation Pharmacology, A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Obninsk, Russian Federation ORCID: https://orcid.org/0000-0003-1329-8312, eLibrary SPIN: 4057-6390, AuthorID: 79952, Scopus Author ID: 57202953931
Competing Interests:
Sergey A. Ivanov, Andrey D. Kaprin is the member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
A. A. Shitova
https://new.nmicr.ru/mrrc/
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
Obninsk, Russian Federation
Anna A. Shitova – Junior Researcher, Laboratory of Radiation Pharmacology, A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Obninsk, Russian Federation ORCID: https://orcid.org/0000-0001-5512-9096, eLibrary SPIN: 6515-6184, Author ID: 1065554, Scopus Author ID: 57220804030, WoS ResearcherID: ABI-5295-2020
Competing Interests:
Sergey A. Ivanov, Andrey D. Kaprin is the member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
V. A. Rybachuk
https://new.nmicr.ru/mrrc/
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
Obninsk, Russian Federation
Vitaly A. Rybachuk – Junior Researcher, Laboratory of Radiation Pharmacology, A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Obninsk, Russian Federation ORCID: https://orcid.org/0000-0001-8820-9965, eLibrary SPIN: 6120-2118, Author ID: 1113883, Scopus Author ID: 57469224000, WoS ResearcherID: ABL-0020-2022
Competing Interests:
Sergey A. Ivanov, Andrey D. Kaprin is the member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
K. A. Nikolaev
https://new.nmicr.ru/mrrc/
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
Obninsk, Russian Federation
Kirill A. Nikolaev – Laboratory Assistant, Laboratory of Radiation Pharmacology, A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Obninsk, Russian Federation ORCID: https://orcid.org/0000-0003-0518-8228, eLibrary SPIN: 9728-1210, Author ID: 1126522, Scopus Author ID: 59121729200, WoS ResearcherID: AGH-3670-2022
Competing Interests:
Sergey A. Ivanov, Andrey D. Kaprin is the member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
A. O. Kosachenko
https://new.nmicr.ru/mrrc/
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
Obninsk, Russian Federation
Aleksandr O. Kosachenko – biologist, Laboratory of Radiation Pharmacology, A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Obninsk, Russian Federation ORCID: https://orcid.org/0000-0003-2173-388X, eLibrary SPIN: 7751-6189, Author ID: 1088023, Scopus Author ID: 57220806815, WoS ResearcherID: ABQ-8315-2022
Competing Interests:
Sergey A. Ivanov, Andrey D. Kaprin is the member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
E. A. Prosovskaya
https://new.nmicr.ru/mrrc/
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
Obninsk, Russian Federation
Ekaterina A. Prosovskaya – Laboratory Assistant, Laboratory of Radiation Pharmacology, A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Obninsk, Russian Federation ORCID: https://orcid.org/0009-0004-0707-0471, eLibrary SPIN: 1033-2434, AuthorID: 1330594
Competing Interests:
Sergey A. Ivanov, Andrey D. Kaprin is the member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
G. A. Demyashkin
https://new.nmicr.ru/mnioi/
P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre
P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre
Moscow, Russian Federation
Grigory A. Demyashkin – Dr. Sci. (Medicine), Head of the Department of Digital Oncomorphology, P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre, Moscow, Russian Federation ORCID: http://orcid.org/0000-0001-8447-2600, eLibrary SPIN: 5157-0177, AuthorID: 645433, Scopus Author ID: 57200415197, WoS ResearcherID: ABD-7650-2021
Competing Interests:
Sergey A. Ivanov, Andrey D. Kaprin is the member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
P. V. Shegai
https://new.nmicr.ru
National Medical Research Radiological Centre
National Medical Research Radiological Centre
Obninsk, Russian Federation
Petr V. Shegai – Cand. Sci. (Medicine), MD, Oncologist, Deputy General Director for Science, National Medical Research Radiological Centre, Obninsk, Russian Federation ORCID: https://orcid.org/0000-0001-9755-1164, eLibrary SPIN: 6849-3221, AuthorID: 708894, Scopus Author ID: 16025544200, WoS ResearcherID: E-9611-2014
Competing Interests:
Sergey A. Ivanov, Andrey D. Kaprin is the member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
S. A. Ivanov
https://new.nmicr.ru/mrrc/
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Obninsk, Russian Federation
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Obninsk, Russian Federation
Peoples’ Friendship University of Russia (RUDN University), Moscow, Russian Federation
Sergey A. Ivanov – Dr. Sci. (Medicine), Corresponding Member of the RAS, Director of A. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Obninsk, Russian Federation; Professor of the Department of Oncology and Radiology named after V.P. Kharchenko at the Medical Institute, Peoples' Friendship University of Russia, Moscow, Russian Federation ORCID: https://orcid.org/0000-0001-7689-6032, eLibrary SPIN: 4264-5167, AuthorID: 710405, Scopus Author ID: 16070399200, WoS ResearcherID: N-8221-2017
Competing Interests:
Sergey A. Ivanov, Andrey D. Kaprin is the member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
A. D. Kaprin
https://new.nmicr.ru
P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre, Moscow, Russian Federation;
P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre, Moscow, Russian Federation;
National Medical Research Radiological Centre, Obninsk, Russian Federation;
Peoples’ Friendship University of Russia (RUDN University), Moscow, Russian Federation
Andrey D. Kaprin – Dr. Sci. (Medicine), Professor, Academician of the Russian Academy of Sciences, Academician of the Russian Academy of Education, Director of P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre, Moscow, Russian Federation, General Director of National Medical Research Radiological Centre, Obninsk, Russian Federation, Head of the Department of Oncology and Radiology named after V.P. Kharchenko at the Medical Institute, Peoples' Friendship University of Russia, Moscow, Russian Federation ORCID: https://orcid.org/0000-0001-8784-8415, eLibrary SPIN: 1759-8101, AuthorID: 96775, Scopus Author ID: 6602709853, WoS ResearcherID: K-1445-2014
Competing Interests:
Sergey A. Ivanov, Andrey D. Kaprin is the member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
A. S. Filimonov
https://new.nmicr.ru/mrrc/
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre
Obninsk, Russian Federation
Aleksandr S. Filimonov – Researcher, Laboratory of Radiation Pharmacology, A.Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Obninsk, Russian Federation ORCID: https://orcid.org/0000-0002-4398-1764, eLibrary SPIN: 3133-2031, Author ID: 85944, Scopus Author ID: 7006442481, WoS ResearcherID: ABC-6039-2020
Competing Interests:
Sergey A. Ivanov, Andrey D. Kaprin is the member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
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Soldatova O.V., Filimonova M.V., Surinova V.I., Shitova A.A., Rybachuk V.A., Nikolaev K.A., Kosachenko A.O., Prosovskaya E.A., Demyashkin G.A., Shegai P.V., Ivanov S.A., Kaprin A.D., Filimonov A.S. Anti-tumor and anti-metastatic properties of bromo- and bis(2-chloroethyl)amino-substituted derivatives of N-methyl ethyl esters of indole-3-carboxylic acid in the S-37 sarcoma mouse model. South Russian Journal of Cancer. 2026;7(1):6-23. (In Russ.) https://doi.org/10.37748/2686-9039-2026-7-1-1. EDN: DCMGEC
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