5,6-Dihydrotetrazolo[1,5-c]quinazolines: Toxicity prediction, synthesis, antimicrobial activity, molecular docking, and perspectives

Antimicrobial resistance is a never-ending challenge, which should be considered seriously, especially when using unprescribed over-the-counter drugs. The synthesis and investigation of novel biologically active substances is among the directions to overcome this problem. Hence, 18 novel 5,6-dihydrotetrazolo[1,5-c]quinazolines were synthesized, their identity, purity, and structure were elucidated by elemental analysis, IR, LC-MS, H-1, and C-13 NMR spectra. According to the computational estimation, 15 substances were found to be of toxicity Class V, two of Class IV, and only one of Class II. The in vitro serial dilution method of antimicrobial screening against Escherichia coli, Staphylococcus aureus, Klebsiella aerogenes, Pseudomonas aeruginosa, and Candida albicans determined b3, c1, c6, and c10 as the lead-compounds for further modifications to increase the level of activity. Substance b3 demonstrated antibacterial activity that can be related to the calculated high affinity toward all studied proteins: 50S ribosomal protein L19 (PDB ID: 6WQN), sterol 14-alpha demethylase (PDB ID: 5TZ1), and ras-related protein Rab-9A (PDB ID: 1WMS). The structure-activity and structure-target affinity relationships are discussed. The targets for further investigations and the anatomical therapeutic chemical codes of drug similarity are predicted.

Automated summary

Antimicrobial resistance is a serious challenge, especially with the misuse of over-the-counter drugs. The synthesis of novel substances, such as 5,6-dihydrotetrazolo[1,5-c]quinazolines, is a potential solution. In this study, 18 new compounds were synthesized and their identity and structure were determined. The antimicrobial screening identified several lead-compounds with potential for further modification to enhance their activity.