Novel 4-methylthienopyrimidines as antimicrobial agents: synthesis, docking study and in vitro evaluation

Sergiy Vlasov Konstantin Krolenko Hanna Severina Olena Vlasova Oleksandr Borysov Pavlo Shynkarenko Vitaliy Vlasov Victoriya Georgiyants   

Open Access   

Published:  Dec 13, 2022

DOI: 10.7324/JAPS.2023.102631
Abstract

Compounds with thieno[2,3-d]pyrimidine core modified with amide group at position five of the heterocyclic system were reported as ligands to bacterial TrmD, which is an enzyme responsible for protein synthesis in bacterial cells and its blockage leads to the death of bacteria or makes them less resistant to antibiotic therapy. The great problem of antibiotic resistance, especially of Gram-negative bacteria like Pseudomonas aeruginosa, forced us to design and study the antimicrobial properties of novel thieno[2,3-d]pyrimidine with amide function at position six as possible bacterial TrmD inhibitors. For the synthesis of the target derivatives with an aromatic pyrimidine cycle and a methyl group at position four, the Suzuki reaction was used. The previously unknown key intermediate 4,5-dimethylthieno[2,3-d] pyrimidine-6-carboxylic acid was further transformed into various novel derivatives of 4-methylthieno[2,3-d] pyrimidines by interaction with amines. The antimicrobial activity screening results show that benzyl amides of 4,5-dimethylthienopyrimidines were the most active, especially against Ba?illus subtilis and P. aeruginosa. The docking studies also revealed that benzylamides showed the best binding parameters to the selective inhibitors’ active site of tRNA (Guanine37-N1)-methyltransferase, an enzyme isolated from P. aeruginosa.


Keyword:     Benzyl amides thienopyrimidine Suzuki reaction antimicrobial activity


Citation:

Vlasov S, Krolenko K, Severina H, Vlasova O, Borysov O, Shynkarenko ?, Vlasov V, Georgiyants V. Novel 4-methylth­ienopyrimidines as antimicrobial agents: synthesis, docking study and in vitro evaluation. J Appl Pharm Sci, 2022. https://doi.org/10.7324/JAPS.2023.102631

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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