The synthesis of mono- and bis-derivatives of spiro-2-oxindole[3,3’]pyrrole and the study of their antioxidant and anti-inflammatory activities
Journal Title: Вісник фармації - Year 2018, Vol 95, Issue 3
Abstract
Aim. To synthesize a series of mono- and bis-derivatives of spiro-2-oxindole[3,3’]pyrrole and study the antioxidant and anti-inflammatory activity of the compounds obtained.Materials and methods. Methods of organic synthesis and instrumental methods for determining the structure of organic compounds were used. The antioxidant properties of the compounds synthesized were studied in vitro on the model of spontaneous lipid peroxidation (LPO); the model of acute aseptic inflammation (carrageenan edema) was used for determination of the anti-inflammatory (anti-exudative) activity.Results and discussion. A series of novel spiro-2-oxindole[3,3’]pyrrole derivatives was synthesized by means of the three-component cascade interaction of isatin, α-amino acids and dipolarophils based on bis-maleimids. In order to broaden the range of compounds obtained nitroso derivatives of ethylene-N,N’-bis(spiroindole-3,3’-pyrrolo[3,4-c]pyrrole-5’-methyl-2a,5a’-dihydro-2,2’,6’(1H,1’H,5’H)-trione) 4 and hexamethylene-N,N’-bis(spiroindole-3,3’-pyrrolo[3,4-c]pyrrole-5’-benzyl-2a’,5a’-dihydro-2,2’,6’(1H,1’H,5’H)-trione) 5 were synthesized. The structure of these compounds was reliably confirmed by instrumental methods (1H NMR, IR-spectroscopy and chromatographic mass spectrometry). The screening studies of the anti-inflammatory properties were conducted, they included the study of the antioxidant action of the compounds synthesized in vitro. Three of the substances tested revealed the highest antioxidant properties and were subsequently selected for further study of their anti-inflammatory activity. The data of the biological experiments showed their pronounced anti-inflammatory properties on the model of carrageenan edema.Conclusions. It has been found that the preparatory method of the three-component cascade transformation of isatin, α-amino acids and dipolarophils based on bis-maleimides is effective for the synthesis of spiro-2-oxindole[3,3’]pyrrole mono- and bis-derivatives. A series of hexamethylene- and ethylene-N,N’-bis(spiroindole-3,3’-pyrrolo[3,4-c]pyrrole-4’-nitroso-2a,5a’-dihydro-2,2’,6’(1H,1’H,5’H)-trione) symmetric derivatives have been obtained. The structure of the compounds obtained has been confirmed. When studying the antioxidant activity of the compounds synthesized it has been found that the most active substances are 1’-(hexamethylene-N-maleimido)-5’-benzyl-2a’,5a’-dihydro-1’H-spiroindole-3,3’-pyrrolo[3,4-c]pyrrole-2,2’,6’(1H,3’H,5’H)-trione 1; ethylene-N,N’-bis(spiroindole-3,3’-pyrrolo[3,4-c]pyrrole-4’-nitroso-5’-methyl-2a,5a’-dihydro-2,2’,6’(1H,1’H,5’H)-trione) 6; hexamethylene-N,N’-bis(spiroindole-3,3’-pyrrolo[3,4-c]pyrrole-4’-nitroso-5’-benzyl-2a,5a’-dihydro-2,2’,6(1H,1’H,5’H)-trione) 7. Compound 6 has also shown the anti-inflammatory activity at the reference drug level.
Authors and Affiliations
Ye. I. Syumka, H. B. Kravchenko, V. P. Chernykh, L. A. Shemchuk
Keywords
Related Articles
- EP ID EP669177
- DOI 10.24959/nphj.18.2217
- Views 77
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