Green synthesis of some new azolopyrimidines as antibacterial agents based on thiophene-chalcone

Abstract

Optimization of green synthesis for a novel pyrazolo[1,5-a]pyrimidines 3a-i, 7a-f, triazolo[4,3-a]pyrimidine 8 and benzo[4,5]imidazo[1,2-a]pyrimidine 9 were synthesized from the reaction of 1-(4-aminophenyl)-3-(thiophen-2-yl)prop-2-en-1-one 1 with 4-arylazo-3,5-diaminopyrazoles 2a-i, 5-amino-N-aryl-3-(phenylamino)-1H-pyrazole-4-carboxamides 6a-f, 3-amino-1,2,4-triazole and 2-aminobenzoimidazole, respectively. A simple approach was used under various conditions to achieve the best conditions for the synthesis. Some new compounds were evaluated for antibacterial activity in vitro, and when compared to traditional antibiotics, they showed good efficacy. The MIC value for pyrazolo[1,5-a]pyrimidine 3d, 3i and 7d in Escherichia coli, Klebsiella pneumonia and Acinetobacter baumannii equal 31.25 µg/L. Better binding patterns were revealed by molecular docking studies for 3d, 3i and 7d with the active site of Escherichia coli DHFR co-crystalized with the active site of trimethoprim [PDB coded 6XG5]. The physicochemical characteristics and toxicity hazards by Osiris methodology besides Swiss ADME predications were performed for all the synthesized compounds exhibiting better biological and antibacterial characters.

Graphical Abstract

Keywords:

• Acinetobacter baumannii
• 1-(4-aminophenyl)-3-(thiophen-2-yl)prop-2-en-1-one
• dihydrofolate reductase (DHFR) escherichia coli
• pyrazolo[1,5-a]pyrimidines
• 1,2,4-triazolo[4,3-a]pyrimidine