Biopolym. Cell. 2024; 40(1):68-80.
http://dx.doi.org/10.7124/bc.000AAB
Bioorganic Chemistry
Synthesis and antibiofilm activity of novel 1,4-dihydropyrido[1,2-a]pyrrolo[2,3-d]pyrimidine-2-carboxamides
1Muzychka L. V., 2Humeniuk N. I., 2Boiko I. O., 2Vrynchanu N. O., 1Smolii O. B.
  1. V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine,
    1, Academician Kukhar Str., Kyiv, Ukraine, 02094
  2. Institute of Pharmacology and Toxicology of National Medical Academy of Science of Ukraine
    14, Anton Tsedyk Str., Kyiv, Ukraine, 03057

Abstract

Aim. Synthesis of novel alkyl-substituted 4-oxo-1,4-dihydropyrido[1,2-a]pyrrolo[2,3-d]pyrimidine-2-carboxamides and evaluation of their antibiofilm activity in vitro. Methods. Organic synthesis, analytical and spectral methods, broth microilution method, biofilm formation on abiotic surface. Results. A simple and efficient method for the synthesis of new 1,4-dihydropyrido[1,2-a]pyrrolo[2,3-d]pyrimidine-2-carboxylic acid derivatives was developed. The results of antibiofilm activity screening showed that among the synthesized alkyl-substituted 1,4-dihydropyrido[1,2-a]pyrrolo[2,3-d]pyrimidine-2-carboxamides there are the compounds capable to disrupt the formation of biofilm of methicillin-resistant strain S. aureus 222, E. coli 311 and P. aeruginosa 449. Compound 6g is active against biofilms of E. coli 311, biomass decreases by 91.2%, and against S. aureus 222 (reduction by 54.0 %). Compound 6d is active against biofilms of P. aeruginosa 449 and S. aureus 222 (reduction by 78.7 % and 50.2 %, respectively). Conclusions. A series of novel substituted 1-alkyl-4-oxo-1,4-dihydropyrido[1,2-a]pyrrolo[2,3-d]pyrimidine-2-carboxamides were synthesized. The activity of the synthesized pyrido[1,2-a]pyrrolo[2,3-d]pyrimidines towards the S. aureus 222, E. coli 311 and P. aeruginosa 449 biofilm formation was investigated, and the compounds with the pronounced antibiofilm activity were found.
Keywords: pyrido[1,2-a]pyrrolo[2,3-d]pyrimidines, pyrido[1,2-a]pyrimidine-3-carbaldehydes, synthesis, antibiofilm activity
Full text: (PDF, in English)

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