d]pyrimidine (1) is a reported pyridothienopyrimidine derivative. In the current study, (1) has been reacted with different reagents to obtain 12 new pyridothienopyrimidine derivatives. The newly synthesized five-membered heterocyclic rings incorporated with pyridothienopyrimidines have been screened for their antibacterial activities. The results encourage further studies on other possible biological activities.

Numerous peptide drugs are currently undergoing advanced phases of clinical testing to determine their efficacy in combating antibiotic-resistant bacterial pathogens. Our aim was to prepare some novel peptides containing a modified pyrazolopyrimidine moiety and assess their activity against a set of selected bacteria in comparison to a widely used antibiotic, ciprofloxacin. In this study, eight new peptide compounds incorporating a modified pyrazolopyrimidine moiety were synthesized. Our results revealed that compounds 4 and 5, which contained only the pyrazolopyrimidine scaffold were less active than the peptide-conjugated pyrazolopyrimidines 10, 11, 13, 14, 15, and 17. The antibacterial activities of the eight novel compounds 4, 5, 10, 11, 13, 14, 15, and 17 were evaluated against a panel of bacterial strains. All the novel compounds exhibited potent antibacterial activity against Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa strains compared to the reference antibiotic ciprofloxacin. The tested Escherichia coli strain displayed resistance against the newly synthesized compounds. Moreover, P. aeruginosa strain displayed resistance against ciprofloxacin and six of the newly synthesized compounds. Compounds 15 and 17 effectively inhibited the growth of the P. aeruginosa strain at MIC ≥ 1 μg/mL. Our results are encouraging and urge additional biological and pharmacological screening of the most active compounds against drug-resistant microbial strains.