Zarenezhad Elham, Behmard Esmaeil, Karami Raziyeh, Behrouz Somayeh, Marzi Mahrokh, Ghasemian Abdolmajid, Soltani Rad Mohammad Navid
Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.
School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran.
BMC Chem. 2024 Dec 18;18(1):244. doi: 10.1186/s13065-024-01333-w.
The antibiotic resistance and biofilm formation by bacterial pathogens has led to failure in infections elimination. This study aimed to assess the antibacterial and anti-biofilm properties of novel synthesized nitroimidazole compounds (8a-8o). In this study, nitroimidazole compounds were synthesized via the A3 coupling reaction of sample substrates in the presence of copper-doped silica cuprous sulfate (CDSCS). Fifteen and two carbapenemase producing Escherichia coli and Klebsiella pneumonia (CP-E. coli and CP-K. pneumonia, respectively) and one methicillin-resistant Staphylococcus aureus (MRSA) and one methicillin-susceptible S. aureus (MSSA) plus standard strain of each isolate were included. The antibacterial effects of these compounds demonstrated that the lowest minimum inhibitory and bactericidal concentrations (MIC/MBC, respectively) levels corresponded to compound 8g against S. aureus (1/2 µg/mL) and K. pneumonia (8/32 µg/mL) standard and clinical strains and confirmed by in silico assessment. This was comparable to those of metronidazole being 32-128 µg/mL against K. pneumonia and 32-64 µg/mL against S. aureus. In comparison to metronidazole, against CP-E. coli, compounds 8i and 8m had significantly higher antibacterial effects (p < 0.001) and against CP-K. pneumonia, compounds 8a-8j and 8l-8o had significantly higher (p < 0.0001) antibacterial effects. Compound 8g exhibited significantly higher antibacterial effects against MSSA and compounds 8b (p < 0.001), 8c (p < 0.001), 8d (p < 0.001), 8e (p < 0.001) and 8g (p < 0.0001) exerted significantly higher antibacterial effects than metronidazole against MRSA. Moreover, potential anti-biofilm effects was corresponded to compounds 8a, 8b, 8c, 8e, 8f, 8g, 8i, 8k, 8m and 8n. Considering the antibacterial and anti-biofilm effects of novel synthesized compounds evaluated in this study, further assessments is warranted to verify their properties in vivo and clinical trials in the future.
细菌病原体的抗生素耐药性和生物膜形成导致感染清除失败。本研究旨在评估新合成的硝基咪唑化合物（8a - 8o）的抗菌和抗生物膜特性。在本研究中，硝基咪唑化合物是在铜掺杂二氧化硅硫酸铜（CDSCS）存在下通过样品底物的A3偶联反应合成的。研究纳入了15株产碳青霉烯酶的大肠杆菌和2株肺炎克雷伯菌（分别为产碳青霉烯酶大肠杆菌和产碳青霉烯酶肺炎克雷伯菌）、1株耐甲氧西林金黄色葡萄球菌（MRSA）和1株甲氧西林敏感金黄色葡萄球菌（MSSA）以及每种分离株的标准菌株。这些化合物的抗菌效果表明，最低最小抑菌浓度和杀菌浓度（分别为MIC/MBC）水平对应于化合物8g对金黄色葡萄球菌标准菌株和临床菌株（1/2 μg/mL）以及肺炎克雷伯菌标准菌株和临床菌株（8/32 μg/mL），并通过计算机评估得到证实。这与甲硝唑对肺炎克雷伯菌的32 - 128 μg/mL以及对金黄色葡萄球菌的32 - 64 μg/mL相当。与甲硝唑相比，对于产碳青霉烯酶大肠杆菌，化合物8i和8m具有显著更高的抗菌效果（p < 0.001），对于产碳青霉烯酶肺炎克雷伯菌，化合物8a - 8j和8l - 8o具有显著更高（p < 0.0001）的抗菌效果。化合物8g对MSSA表现出显著更高的抗菌效果，并且化合物8b（p < 0.001）、8c（p < 0.001）、8d（p < 0.001）、8e（p < 0.001）和8g（p < 0.0001）对MRSA的抗菌效果显著高于甲硝唑。此外，潜在的抗生物膜效果对应于化合物8a、8b、8c、8e、8f、8g、8i、8k、8m和8n。考虑到本研究中评估的新合成化合物的抗菌和抗生物膜效果，有必要进一步评估以验证它们在未来体内和临床试验中的特性。
