Esters of thiosulfonic acids, both synthetic and natural, are the subject of ongoing research in organic, pharmaceutical and medical chemistry, as they are promising biologically active substances with a wide range of biological effects. They demonstrate antitumor, antiviral activity and a wide range of antimicrobial activity, have a positive effect on the cardiovascular system, in particular the substances showing potential antithrombotic activity in vitro .
Potential anti-cancer agents are known compounds of the phthalimide moiety, since phthalimides are well known cytotoxic intercalators of DNA.
Substances with phtalimide particle are admitted as potential anti-cancer agents, whereas phthalimides well khown as cytotoxic intercalators of DNA.
Targeting to find new biologically active compounds - promising substances for the synthesis of new pharmaceuticals of various uses, it is essential to synthesize previously not discovered S-phthalimidaalkyl esters of 4-substituted benzethiosulfonic acids.
Sodium 4-substituted benzethiosulfonates were used as initial compounds for the synthesis of the target products of S-phthalimidoalkyl esters of 4-substituted benzethiosulfonic acids. In the reaction of the nucleophilic substitution of the bromine side atoms of the 2- (3-bromo-ethyl) -isoindole-1,3-dione or 2- (2-bromopropyl) -isoindole-1,3-dione to the thiosulfonate fragment.
As a result, preparative methods for the interaction of salts of aromatic thiosulfonic acids with phthalimidalkyl derivatives were proposed. The physical-chemical characteristics of synthesized thiosulfonate derivatives with phthalimidalkyl fragment were disclosed using modern research methods.
To intensify process, at the initial stage of the search for pharmacologically active substances, the authors used new modern approaches to the organization of researches.
Using the in silico method, namely the PERS (Prediction of Activity Spectra for Substances) program, the direction of further experimental biological research of synthesized compounds was established for those types of biological activity selected by the program mentioned above. The promises of new thiosulfoesters as inhibitors of various enzymes are presented, and these compounds can be promising in the research for new antitumor, antithrombotic and antiviral substances.
1. Foskolos A., Siurana A., Rodriquez-Prado M., Ferret A., Bravo D. and Calsamiglia S. / The
effects of a garlic oil chemical compound, propyl-propane thiosulfonate, on ruminal fermentation and fatty
acid outflow in a dual-flow continuous culture system // J. Dairy Sci. – 2015. – Vol. 98 – Р. 1–10.
2. Galván J. E., Contreras Aguilar E., Defonsi Lestard M. E., Tuttolomondo M. E., Ulic S. E., Ben
Altabef A. Theoretica and experimenta study of a new thiosulfonate derivative: methyl
trifluoromethanethiosulfonate, CF3SO2SCH3. Conformational transferability in CX3SO2S-R compounds //
Inorganica Chimica Acta. – 2017. – Vol. 455, Part 1. – P. 254–261. 3. Gabriele Elena, Brambilla Dario,
Ricci Chiara, Regazzoni Luca, Taguchi Kyoko, Ferri Nicola, Akira Asai & Anna Sparatore / New
sulfurated derivatives of cinnamic acids and rosmaricine as inhibitors of STAT3 and NF-κB transcription
factors // Journal of Enzyme Inhibition and Medicinal Chemistry. – 2017. – Vol. 32, No. 1 – P. 1012–1028.
4. Elena Gabrielea, Chiara Riccib, Fiorella Meneghettia, Nicola Ferric, Akira Asaid and Anna Sparatorea /
Methanethiosulfonate derivatives as ligands of the STAT3-SH2 domain //Journal of enzyme inhibition and
medicinal chemistry. – 2017. – Vol. 32, No. 1. – Р. 337–344/ 5. Lubenets V., Parashchyn Z., Vasylyuk S.,
Novikov V. / The S-methyl-(2-methoxycarbonylamino-benzimidazole-5) thiosulfonate as potential
anticancer agents // Global journal of Pharmacy & pharmaceutical Science. – 2017. – Vol. 3, №2. –
P. 001–00. 6. Toshihiro Nohara, Yukio Fujiwara, Mona El-Aasr, Tsuyosh Ikeda, Masateru Ono, Daisuke
Nakano, Junei Kinjo / Antitumor Allium Sulfides // Chem. Pharm. Bull. – 2017. – Vol. 65 – P. 209–217.
7. Vira Lubenets, Sofiya Vasylyuk, Nataliya Monka, Khrystyna Bolibrukh, Olena Komarovska-
Рorokhnyavets, Diana Baranovych, Rostyslav Musyanovych, Ewa Zaczynska, Anna Czarny, Urszula
Nawrot, Volodymyr Novikov / Synthesis and antimicrobial properties of 4-acylaminobenzenethiosulfoacid
S-esters // Saudi Pharmaceutical Journal. – 2017 – Vol. 25, No. 2. – P. 266–274. 8. Nawrot U, Zaczyńska E.,
Czarny A, Lubenets V, Karpenko E. / Antifungal activity of synthetic derivatives of allicin – continued
research. // Mikologia Lekarska. – 2012. – 19(4). – Р. 143–14. 9. Anna Sotirova, Tatyana Avramova,
Stoyanka Stoitsova, Irina Lazarkevich, Vera Lubenets, Elena Karpenko, Danka Galabova / The importance
of rhamnolipid- biosurfactant induced changes in bacterial membrane lipids of Bacillus subtilis for the
antimicrobial activity of thiosulfonates // Curr. Microbiol. – 2012. – Vol. 65, No. 5. – P. 534–541. 10. Use
of antimicrobial agents derved fromalliaceous plants for the prevention and control of crop diseases, postharvest
rot and as environmental disinfectant products: IPC8 Class: AA01N4104FI; USPC Class: 514553 /
Maria Pilar Garcia-Pareja, Eduardo Sanchez-Vaquero, Enrique Guillamon Ayala, Felix Martinez Lopez –
№ 20090018194; Publication date: 2009-01-15. 11. T. I. Halenova, I. V. Nikolaeva, A. V. Nakonechna,
K. B. Bolibrukh, N. Y. Monka, V. I. Lubenets, O. M. Savchuk, V. P. Novikov, L. I. Ostapchenko / The search
of compounds with antiaggregation activity among S-esters of thiosulfonic acids // Ukr. Biochem. J. –
2015. – Vol. 87, No. 5. – P. 83–92. 12. Kh. Bolibrukh, S. Polovkovych, O. Khoumeri, T. Halenova,
I. Nikolaeva, O. Savchuk, T. Terme, P. Vanelle, V. Lubenets, V. Novikov / Synthesis and anti-platelet
activity of thiosulfonate derivatives containing a quinone moiety // Scientia Pharmaceutica. – 2015. –
127
Vol. 83. – P. 221–231. 13. L. Oriabinska, S. Starovoitova, S. Vasylyuk, V. Novikov, V. Lubenets /
Ethylthiosulfanilate effect on Candida tropicalis // Ukr. Biochem. J. – 2017. – Vol. 89, No. 5. – P. 70–76.
14. Paloma Abad, Natalia Arroyo-Manzanares, Lidia Gil, and Ana M. García-Campaña / Use of Onion
Extract as a Dairy Cattle Feed Supplement: Monitoring Propyl Propane Thiosulfonate as a Marker of Its
Effect on Milk Attributes // J Agric Food Chem. 2017 Feb 1; 65(4), – Р. 793–799. 15. Pranab K. Shyam
and Hye-Young Jang / Synthesis of Sulfones and Sulfonamides via Sulfinate Anions: Revisiting the Utility
ofThiosulfonates // J. Org. Chem. – 2017. – 82 (3). – Р. 1761–1767. 16. Peng-Fei Cheng, Chao-Jie Wang
and Yu-Xia Wang / 2-(3-Bromopropyl) isoindoline-1,3-dione // Acta Cryst.(2009), E 65. – Р. 02646.
17. M. F. Braña and A. Ramos/ Naphthalimides as Anticancer Agents: Synthesis and Biological Activity //
Curr. Med. Chem. – Anti-Cancer Agents. – 2001. – 1. – Р. 237–255. 18. Yuichiro Tsuchiya, Danielle
Vidaurre, Shigeo Toh, Atsushi Hanada, Eiji Nambara, Yuji Kamiya, Shinjiro Yamaguchi & Peter McCourt
/ А small-molecule screen identifies new functions for the plant hormone strigolactone / Nature Chemical
biology. – 2010. – Vol. 6. – P. 741–749. 19. Sofiya Vasylyuk, Olena Komarovska-Porokhnyavets,
Volodymyr Novikov, Vira Lubenets Modification of Alkyl Esters of 4-Aminobenzenethiosulfonic Acid by s-
Triazine Fragment and Investigation of their Growth-Regulative Activity // Сhem Chem Technol. 2018;
7(1): 24-2810.23939/chcht12.01.024. 20. Lubenets V., Karpenko O., Ponomarenko M., Zahoriy G.,
Krychkovska A., Novikov V. Development of new antimicrobial compositions of thiosulfonate structure.
Сhem Chem Technol. – 2013. – 7(2). – 119–124. 21. Швець В. В., Карпенко О. В., Лубенець В. І.,
Новіков В. П. / Антимікробна активність композицій на основі тіосульфонатів і біогенних
поверхнево-активних речовин щодо фітопатогенів // Наукові вісті Національного технічного
університету України “Київський політехнічний інститут”. – 2017. – № 3. – C. 89–94. 22. Field L.,
Aldo F., Crenshaw R., Owen C. / Organic disulfides and related substances. IX. Symmetrical
aminothiolsulfinates as antiradiation drugs // J. Med. Chem. – 1964. – Vol. 39, No. 7. – P. 39–44.
23. Суворова Н. Н., Шашков В. С. Химия и фармакология средств профилактики радиационных
поражений. – М.: Атомиздат, 1975. – C. 224. 24. Н. Я. Монька, С. В. Василюк, А. В. Наконечна,
Д. Б. Баранович, Г. Б. Шиян, В. І. Лубенець / Cинтез s-естерів 4-фталімідометилбензентіосульфо-
кислоти / Вісник Національного університету “Львівська політехніка” “Хімія, технологія речовин
та їх застосування”. – 2015. – № 812. – С. 274–280. 25. A. Lagunin, A. Stepanchikova, D. Filimonov,
V. Poroikov / PASS: prediction of activity spectra for biologically active substances // Bioinformatics. –
2000. – Vol. 16(8). – P. 747–748.