N₄‐benzyl‐N₂‐phenylquinazoline‐2,4‐diamine compound presents antibacterial and antibiofilm effect against Staphylococcus aureus and Staphylococcus epidermidis

Abstract

Staphylococcus aureus and Staphylococcus epidermidis are the main agents involved with implant-related infections. Their ability to adhere to medical devices with subsequent biofilm formation is crucial to the development of these infections. Herein, we described the antibacterial and antibiofilm activities of a quinazoline-based compound, N 4-benzyl-N 2-phenylquinazoline-2,4-diamine, against both biofilm-forming pathogens. The minimum inhibitory concentrations (MIC) were determined as 25 µM for S. aureus and 15 µM for S. epidermidis. At sub-MIC concentrations (20 µM for S. aureus and 10 µM for S. epidermidis), the compound was able to inhibit biofilm formation without interfere with bacterial growth, confirmed by scanning electron microscopy. Moreover, surfaces coated with the quinazoline-based compound were able to prevent bacterial adherence. In addition, this compound presented no toxicity to human red blood cells at highest MIC 25 µM and in vivo toxicity assay using Galleria mellonella larvae resulted in 82% survival with a high dose of 500 mg/kg body weight. These features evidence quinazoline-based compound as interesting entities to promising applications in biomedical fields, such as antimicrobial and in anti-infective approaches.

Synthesis and anti- Toxoplasma activity of indole-triazole compounds on tachyzoites of RH strain

“…However, this effect was greater in benzyl compounds (A) than in naphthalene compound (B), which may be due to its smaller structure and thus greater penetration into the parasite. Also, in various studies, the role and effect of benzyl-containing compounds on various microorganisms and parasites have been confirmed [ [26] , [27] , [28] , [29] ], as in our study, the benzyl derivative showed an ability of over 80% in eliminating Toxoplasma tachyzoites. The main proposed mechanism of action by benzyl compounds may be impaired macromolecular biosynthesis and cell death.…”

Virulence alterations in staphylococcus aureus upon treatment with the sub-inhibitory concentrations of antibiotics

“…Escober et al demonstrated that the nuclear factor-kappa B inhibitor N-[3,5-Bis(trifluoromethyl) phenyl]-5-chloro-2-hydroxybenzamide at sub-MIC of 0.0313 μg/mL can inhibit the initial cell attachment and biofilm formation of vancomycin-resistant S. aureus strain VRS1 in a dose-dependent manner [68] . The sub-MICs of other antimicrobial compounds, such as N-nonyloxypentyl-L-DNJ, N4-benzyl-N-2-phenylquinazoline-2,4-diamine, terpenoid (+)-nootkatone, chitosan, marine steroid siphonocholin, zinc oxide, and silver nanoparticles, are found to be able to inhibit the biofilm formation of diverse S. aureus strains [43] , [46] , [69] , [70] , [71] , [89] .…”

8‐hydroxyquinoline and quinazoline derivatives as potential new alternatives to combat Candida spp. biofilm

“…Two compounds were used, a quinazoline derivative (PH100, N 4 -benzyl-N 2 -phenylquinazoline-2,4-diamine) and an 8-hydroxyquinoline derivative (PH157, N-(3,4dichlorophenyl)-8-hydroxyquinoline-5-sulfonamide), synthesized by the 'Pharmaceutical Synthesis Group'. PH100 is described by Dos Reis et al (2020), and PH157 was synthesized according to the protocol described by Joaquim et al (2019). Stock solutions were prepared in DMSO (Sigma-Aldrich) so that when diluted in the assay medium, a maximum DMSO concentration of 2% was obtained.…”