In vitro antimicrobial activity evaluation of 2-amino-3-r-6-ethyl-4,6-dihydropyrano[3,2-c][2,1] benzothiazine 5,5-dioxides with 4-aryl substituent and spirofused with 2-oxoindoline core

D. A. Lega, N. I. Filimonova, H. M. Dikaya, V. P. Chernykh, L. A. Shemchuk

Abstract


Currently, antibiotic resistance is becoming a tremendous threat in treatment of bacterial and fungal infections. Therefore, a topical question is the search of new classes of antimicrobial drugs. The present article is devoted to the study of antimicrobial activity of 2-amino-3-R-6-ethyl-4,6-dihydropyrano[3,2-c][2,1]benzothiazine 5,5-dioxide derivatives comprising 4-aryl substituent and spirocondensed with 2-oxindole core. Such choice is caused by a high level of antimicrobial activity of some 2-amino-4-aryl-4H-pyran and 2-oxindole derivatives as was reported previously. Microbiological screening of 4-aryl-4H-pyrans showed the high antifungal activity for some derivatives, among which 2-amino-3-cyano-4-(4-dimethylaminophenyl)-6-ethyl-4,6-dihydropyrano[3,2-c][2,1]benzothiazine-5,5-dioxide had the lowest value of MIC. Spirocondensed derivatives of 2-oxindole displayed a higher antimicrobial influence as compared to 4-aryl substituted products. Compounds, that possess moderate antimicrobial activity against B. subtilis and P. aeruginosa as well as antifungal activity against C. albicans, were found among spiro-compounds. The lead compound appeared to be spiro[(2-amino-3-cyano-6-ethyl-4,6-dihydropyrano[3,2-c][2,1]benzothiazine-5,5-dioxide)-4,3'-(1'-methyl-indolin-2'-one)], which was effective against B. subtilis, P. aeruginosa and C. albicans. The results of microbiological screening are discussed from a perspective of «structure – antimicrobial activity» relationships.

Keywords


2;1-benzothiazin 2;2-dioxide; antimicrobial activity; benzaldehydes; isatins; active methylene nitriles; 4H-pyranes; spiro-compounds; three-component reaction

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References


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DOI: https://doi.org/10.24959/89423

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