Synthesis and in vitro evaluation of antibacterial and antibiofilm activities of novel triphenylphosphonium-functionalized substituted pyrimidines.

The increase in the prevalence of antibiotic-resistant pathogens leads to a decrease in the number of antimicrobial agents for the treatment of infections and prompts researchers to search for new effective antimicrobial drugs. This study reports the synthesis of novel triphenylphosphonium-functionalized substituted pyrimidines and in vitro evaluation of their antibacterial and antibiofilm activity. Most of the synthesized derivatives showed high antibacterial activity (MIC = 0.39-1.56 µg/mL) against the methicillin-resistant strain of S. aureus 222. Compounds 2a and 11 exhibited a high level of antibiofilm activity against S. aureus 222 and E. coli 311. The triphenylphosphonium-containing pyrimidines 11 and 2a reduced S. aureus 222 biofilm formation by 99.1% and 95.8%, respectively. In addition, compound 2a was the most active against E. coli 311 biofilm formation (the biomass decreased by 98.4%).

Synthesis, QSAR modeling, and molecular docking of novel fused 7-deazaxanthine derivatives as adenosine A2A receptor antagonists.

Predictive QSAR models for the search of new adenosine A2A receptor antagonists were developed by using OCHEM platform. The predictive ability of the regression models has coefficient of determination q2  = 0.65-0.71 with cross-validation and independent test set. The inhibition activities of novel fused 7-deazaxanthine compounds were predicted by the developed QSAR models. A preparative method for the synthesis of pyrimido[5',4':4,5]pyrrolo[1,2-a][1,4]diazepine derivatives was developed, and 11 new adenosine A2A receptor antagonists were obtained. Preliminary investigations into the toxicology of fused 7-deazaxanthine compounds toward commonly used model organism to assess toxicity invertebrate cladoceran D. magna were also described.