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 National University of Pharmacy
  • N. I. Filimonova National University of Pharmacy
  • H. M. Dikaya National University of Pharmacy
  • V. P. Chernykh National University of Pharmacy
  • L. A. Shemchuk National University of Pharmacy



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


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.

Author Biography

D. A. Lega, National University of Pharmacy

Organic chemistry department


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Microbiological research