Virtual screening and antibacterial activity of lead compounds targeting to penicillin-binding protein 3 (PBP3) of Pseudomonas aeruginosa

Abstract:

[Objective] This study was carried out to obtain lead compounds targeting penicillin-binding protein 3 (PBP3) of Pseudomonas aeruginosa by virtual screening. [Methods] UCSF dock 6.5 was used for the virtual screening from a database containing 1.04 million small molecules. Hit compounds with simple structures were synthesized and then evaluated for their antibacterial activities. [Results] Grid score was used for the first round of screening, and 60000 small molecules whose scores lower than -30 kcal/mol were screened out from the database. These molecules were subjected to the second round of screening using amber score. Approximately 200 hit compounds with scores lower than -20 kcal/mol were analyzed and 4 of them were selected as lead compounds and then synthesized. The minimal inhibition concentrations (MICs) of the lead compounds were between 175-275 μg/mL, which were lower than that of Sulfadiazine (500 μg/mL) significantly. Meanwhile, these compounds were effective for both Gram-negative and Gram-positive bacteria. [Conclusion] The lead compounds had potential to become new antibacterial agents for conquering the drug resistance of P. aeruginosa.