SYNTHESIS AND BIOLOGICAL ACTIVITY OF 5-AMINOMETHYLENE-2-THiOXOTIAZOLIDIN-4-ONES DERIVATIVES
DOI:
https://doi.org/10.11603/2312-0967.2017.2.7876Keywords:
5-aminomethylene-2-thioxothiazolidin-4-ones, spectral characteristics, antitripanosomal, antimicrobial, antitumor activity.Abstract
The aim of the work. Synthesis of 5-aminomethylene-2-thioxothiazolidine-4-ones derivatives as promising compounds for chemical transformations and pharmacological screening.
Materials and methods. The key starting reagents synthesized by known methods from commercially available reagents. The NMR spectra of the synthesized compounds were taken on a Varian VXR-400 instrument, DMSO-d6 solvent, tetramethylsilane standard. LC-MS spectra were obtained on a Finnigan MAT INCOS-50 instrument. Elemental analysis for carbon, hydrogen and nitrogen content corresponds to the calculated (± 0.3%). The melting points were determined on a BŰCHI B-545 apparatus. The study of the antitripanosomal activity of compounds in vitro was carried out at the Museum National d'Histoire Naturelle (France) and consisted in the determination of IC50 on the strain Trypanosoma brucei brucei (TBB). The study of antimicrobial activity in vitro was carried out by diffusion into agar. Determination of the antitumor activity of synthesized compounds was carried out within the framework of the international scientific program DTP (Developmental Therapeutic Program) of the National Cancer Institute (NCI, Bethesda, Maryland, USA).
Results and discussion. Based on the previously proposed synthetic approach to 5-R,R'-aminomethylene-4-thiazolidinones, series of 5-aminomethylene-2-thioxothiazolidine-4-one derivatives were obtained. An effective method for the synthesis of 5-aminomethylene-2-thioxothiazolidin-4-one was proposed based on the aminolysis of the corresponding 5-ethoxymethylene derivative under the action of ammonium hydrogen carbonate in an alcoholic medium. The reactivity of 5-phenyl-3,4-dihydro-2H-pyrazole-3-carboxylic acid in the aminolysis reaction with 5-ethoxymethylene-2-thioxothiazolidin-4-one was investigated for the first time. The structure of synthesized compounds were confirmed by a complex of NMR and mass spectrometric methods. In vitro antitripanosomal, antimicrobial and antitumor activities of synthesized compounds were studied.
Conclusions. Some synthetic methods were proposed and raw of original derivatives of 5-aminomethylene-2-thioxothiazolidine-4-one as promising reagents for chemical transformations and potential objects for pharmacological screening are obtained. Hit-compounds have been identified for the design of potential antitripanosomal and antimicrobial agents.
References
Lesyk RB, Zimenkovsky BS. 4-Thiazolidones: Centenarian history, current status and perspectives for modern organic and medicinal chemistry. Curr Org Chem 2004;8:1547-77.
Fu H, Hou X, Wang L, Dun Y, Yang X, Fang H. Design, synthesis and biological evaluation of 3-aryl-rhodanine benzoic acids as antiapoptotic protein bcl-2 inhibitors. Bioorg Med Chem Lett. 2015;25:5265-9.
Tomasic T, Kovac A, Simcic M, Blanot D, Grdadolnik S, Gobec S, et al. Novel 2-Thioxothiazolidin-4-one inhibitors of bacterial MurD ligase targeting D-glu- and diphosphate-binding. Sites Eur J Med Chem. 2011;46:3964-75.
Golota S, Trufin Ya, Shylych Ya, Derkach G, Kutsyk R, Zimenkovsky B, et al. 5-Ethoxymenylidene moiety as a useful tool for design of biologically active molecules among 4-thia-zolidinone derivatives. Modern Directons in Chemistry, Biology, Pharmacy and Biotechnology, Lviv. 2015;71-5.
Derkach G, Golota S, Zasidko V, Soronovych I, Kutsyk R, Lesyk R. Synthesis and study of antimicrobial properties of 5-R,R'-aminometylene derivatives of thiazolidine-2,4-dione and 4-thioxothiazolidine-2-one. J Org Pharm Chem. 2016;3(55):32-7.
Boyd M, Paull K. Some practical considerations and applications of the national cancer institute in vitro anticancer drug discovery screen. Drug Development Research. 199;34:91-109.
Alley M, Scudiere D, Monks A, Hursey M, Czerwinski M, Fine D, et al. Feasibility of drug screening with panels of humantumor cell lines using a microculture tetrazolium assay. Cancer Research. 1988;48:589-601.
Grever M, Schepartz S, Chabner B. The national cancer institute: cancer drug discovery and development program. Seminars in Oncology. 1992;6:622-38.
Shoemaker R. The NCI60 human tumour cell line anticancer drug screen. Nature Reviews Cancer. 2006;6:813-23.
Lo Ch.-P, Croxall W. 5-Alkoxymethylenerhodanines and their Reactions with Rhodanines. JACS. 1954;76:4166-9.
Havrylyuk D, Roman O, Lesyk R. Synthetic approaches, structure activity relationship and biological applications for pharmacologically attractive pyrazole/pyrazoline-thiazolidine-based hybrids. Eur J Med Chem. 2016;113:145-66.
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