Pyrazolo[5,1‐b]quinazolines and Their Bis‐analogues Linked to Different Spacers: Regioselective Synthesis, Antibacterial Screening and SwissADME Prediction Study

Abstract

The regioselective synthesis of a new series of pyrazolo [5,1b]quinazolines was carried out using a three-component protocol. The protocol involved the reaction of the appropriate benzaldehydes, dimedone, and 1H-pyrazole-3,5-diamine in DMF at 150 °C. Using a similar protocol, three additional series of bis(pyrazolo[5,1-b]quinazolines), linked to different spacers, were prepared utilizing the respective bis(aldehydes). The new products showed a wide spectrum of antibacterial activity against six different the American Type Culture Collection (ATCC) bacterial strains. In general, p-xylene-linked bis(pyrazolo[5,1-b]quinazolines) had good antibacterial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values up to 8.3 and 16.6 μM, respectively. Additionally, (4-nitrophenyl)-linked pyrazolo[5,1b]quinazoline had the best antibacterial activity with MIC/MBC values up to 2.1/4.3 μM. The Salmonella typhimurium reverse mutation assay (Ames mutagenicity test) was used to conclude that the (4-nitrophenyl)-linked product was not mutagenic to the Salmonella strains. Both the drug-likeness model score and the SwissADME predict the (4-nitrophenyl)-linked product's good physicochemical properties, and drug likeness.