DOI: https://doi.org/10.24959/ophcj.19.181138

Chemical transformations of new mono- and bis-derivatives of spiroindol-3,3’-pyrrolo[3,4-c]pyrrole based on bis-maleiminides and the study of the microbiological activity of the compounds synthesized

Ye. I. Siumka, K. M. Sytnik, D. V. Levashov, T. V. Spychak, V. D. Horiachyi, L. A. Shemchuk

Abstract


Aim. To synthesize new derivatives based on hexamethylene(ethylene)-N,N’-bis(spiroindole-3,3’-pyrrolo-[3,4-c]pyrrole-2a,5a’-dihydro-2,2’,6’(1H,1’H,5’H)-trions) and 1’-(m-phenylene-N-maleimidido)-2a’,5a’-dihydro-1’H- spiroindole-3,3’-pyrrolo[3,4-c]pyrrole-2,2’,6’(1H,1’H,5’H)-trions by modifying the NH-group of the pyrrole moiety in position 4’ (alkylation, acylation, nitrosation) and study their microbiological activity.
Results and discussion. The possibility of further chemical modification of the derivatives of hexamethylene(ethylene)-N,N’-bis(spiroindole-3,3’-pyrrolo[3,4-c]pyrrole-2a’,5a’-dihydro-2,2’,6’(1H,1’H,5’H)-trion) has been developed on the example of ethylene-N,N’-bis(spiroindole-3,3’-pyrrolo[3,4-c]pyrrol-5’-methyl-2a’,5a’-dihydro-2,2’,6’(1H,1’H,5’H)-trion), ethylene-N,N’-bis(spiroindole-3,3’-pyrrolo[3,4-c]pyrrole-5’-isopropyl-2a’,5a’-dihydro-2,2’,6’(1H,1’H,5’H)-trione), 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)-trion) and 1’-(m-phenylene-N-maleimidido)-2a’,5a’-dihydro-1’H-spiroindole-3,3’-pyrrolo[3,4-c]pyrrole-5’-methyl-2,2’,6’(1H,1’H,5’H)-trione by modification of the NH-group of the pyrrole fragment in position 4’ (nitrosation) or the NH-group of the indole fragment in position 1 (alkylation), or acylation at once in two positions. The structure of the compounds obtained has been reliably confirmed by instrumental methods. Data from the microbiological screening show a high biological effect of the compounds synthesized in relation to gram-positive (Staphylococcus aureus, Bacillus subtilis), gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris) and fungi (Candida albicans).
Experimental part. The synthesis of the initial and target compounds in classical preparative conditions was performed; instrumental methods for determining the structure of organic compounds, the agar diffusion method in the modification of wells were used.
Conclusions. The chemical modification of mono- and bis-derivatives of spiro-2-oxindole[3,3’]pyrrole has been performed: new functionalized nitroso derivatives have been synthesized, the alkylation reaction has been performed, and the reaction of acylation has been studied. It has been shown that the acylation occurs immediately in two positions – by the secondary amino group of the pyrrole and indole fragments, while the alkylation proceeds by the indole fragment. The structure of the compounds obtained has been proven. The antimicrobial effect of the compounds synthesized has been studied.

Keywords


bis-spirocyclic systems; 2-oxindole; alkylation; acylation; nitrosation; antimicrobial activity

References


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