Synthesis and evaluation of di-heterocyclic benzazole compounds as potential antibacterial and anti-biofilm agents against Staphylococcus aureus.
Mine Buga AktekinZehra OksuzBurcin TurkmenogluErman Salih IstifliMehmet KuzucuOztekin AlgulPublished in: Chemical biology & drug design (2024)
Cumulative escalation in antibiotic-resistant pathogens necessitates the quest for novel antimicrobial agents, as current options continue to diminish bacterial resistance. Herein, we report the synthesis of di-heterocyclic benzazole structures (12-19) and their in vitro evaluation for some biological activities. Compounds 16 and 17 demonstrated potent antibacterial activity (MIC = 7.81 μg/mL) against Staphylococcus aureus, along with significant anti-biofilm activity. Noteworthy is the capability of Compound 17 to inhibit biofilm formation by at least 50% at sub-MIC (3.90 μg/mL) concentration. Furthermore, both compounds exhibited the potential to inhibit preformed biofilm by at least 50% at the MIC concentration (7.81 μg/mL). Additionally, Compounds 16 and 17 were examined for cytotoxic effects in HFF-1 cells, using the MTT method, and screened for binding interactions within the active site of S. aureus DNA gyrase using in silico molecular docking technique, employing AutoDock 4.2.6 and Schrödinger Glidse programs. Overall, our findings highlight Compounds 16 and 17 as promising scaffolds warranting further optimization for the development of effective antibacterial and anti-biofilm agents.
Keyphrases
- staphylococcus aureus
- biofilm formation
- molecular docking
- pseudomonas aeruginosa
- candida albicans
- escherichia coli
- methicillin resistant staphylococcus aureus
- silver nanoparticles
- induced apoptosis
- public health
- cystic fibrosis
- molecular dynamics simulations
- anti inflammatory
- oxidative stress
- cell cycle arrest
- clinical trial
- gram negative
- cell free
- signaling pathway
- circulating tumor
- single molecule
- essential oil
- climate change
- endoplasmic reticulum stress