Synthesis, Antimicrobial Activities, and Model of Action of Novel Tetralone Derivatives Containing Aminoguanidinium Moiety.

The objectives of this study were to design, synthesize, and evaluate the antibacterial activity of a series of novel aminoguanidine-tetralone derivatives. Thirty-four new compounds were effectively synthesized through nucleophilic substitution reaction and guanidinylation reaction. Chemical structures of all the desired compounds were identified by NMR and HR-MS spectroscopy. Most of the synthesized compounds showed significant antibacterial activity against ESKAPE pathogens and clinically resistant () isolates. is an important pathogen that has the capacity to cause a variety of diseases, including skin infections, pneumonia, and sepsis. The most active compound, , showed rapid bactericidal activity against ATCC 29213 and MRSA-2 with MIC/MBC values of 0.5/4 µg/mL and 1/4 µg/mL, respectively. The hemolytic activity and cytotoxicity of was low, with HC and IC values of 50.65 µg/mL and 13.09 µg/mL, respectively. Compound induced the depolarization of the bacterial membrane and disrupted bacterial membrane integrity, ultimately leading to death. Molecular docking revealed that dihydrofolate reductase (DHFR) may be a potential target for . In the mouse skin abscess model caused by MRSA-2, reduced the abscess volume, decreased bacterial load, and alleviated tissue pathological damage at doses of 5 and 10 mg/kg. Therefore, compound may be a promising drug candidate for antibacterial purposes against .