Electrochemical Modification of Metronidazole and its Application as Antibacterial and Potential Drug Agent

IF 1.2 4区 医学 Q4 CHEMISTRY, MEDICINAL
Samuel Attah Egu, Sunday Okpanachi Idih, Favour Idih, Ruth Foluke Aminu, Lawrence Achimugu, Aminu Omale, Jamila Audu Omale, Lian Ojotule Abah, Emmanuel Amlabu
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Abstract

Background: Drug resistance poses a threat to global health given the disturbing rate at which microbiological illnesses are rising and the widespread use of antibiotics. While naturally occurring antibiotics reduce the likelihood of bacterial resistance, recognized drugs can develop the same properties when structurally modified. Metronidazole has been targeted to achieve this feat. Objective: The purpose of this work is to enable the structural modification of metronidazole by means of electric current, using inexpensive, easily accessible magnesium ribbon as electrodes in order to produce a novel, effective antibiotic. Method: With magnesium ribbon electrodes, metronidazole is modified electrochemically, in an undivided cell system. Ultraviolet-visible (UV-Vis), Fourier Transform Infrared (FTIR), and Gas Chromatography-Mass Spectrometry (GC-MS) were used to characterize the product. Antibacterial activity was evaluated using the agar well diffusion method and Wistar rats were used for in vivo toxicity assessment. Result: 2-Methyl-1-vinyl-1H-imidazol-5-amine showed good antibacterial activities compared to the standard nitrofurantoin and toxicity evaluations using Wistar rats revealed that the product might induce dose-dependent variations in kidney function biomarkers, with doses of 100 mg/kg and below. However, when the compound was administered orally, there was no significant effect on liver function, even at a dose of 1000 mg/kg. Conclusion: These results point to the modified metronidazole's potential as a potent antibiotic with controllable toxicity, indicating that additional research into its pharmacological uses is necessary.
甲硝唑的电化学改性及其作为抗菌剂和潜在药物的应用
背景:鉴于微生物疾病的上升速度令人不安,以及抗生素的广泛使用,耐药性对全球健康构成了威胁。虽然天然抗生素能降低细菌产生耐药性的可能性,但公认的药物在经过结构改造后也能产生同样的特性。甲硝唑就是为实现这一目标而研制的。目标:这项工作的目的是利用价格低廉、易于获得的镁带作为电极,通过电流对甲硝唑进行结构改造,从而生产出一种新型、有效的抗生素。研究方法利用镁带电极,在不分裂的细胞系统中对甲硝唑进行电化学改性。使用紫外可见光(UV-Vis)、傅立叶变换红外(FTIR)和气相色谱-质谱法(GC-MS)对产品进行表征。采用琼脂井扩散法评估了产品的抗菌活性,并对 Wistar 大鼠进行了体内毒性评估。结果:与标准的硝基呋喃妥因相比,2-甲基-1-乙烯基-1H-咪唑-5-胺显示出良好的抗菌活性,而使用 Wistar 大鼠进行的毒性评估显示,当剂量为 100 毫克/千克及以下时,该产品可能会引起肾功能生物标志物的剂量依赖性变化。不过,在口服该化合物时,即使剂量为 1000 毫克/千克,也不会对肝功能产生明显影响。结论这些结果表明,改良甲硝唑有可能成为一种毒性可控的强效抗生素,因此有必要对其药理用途进行进一步研究。
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来源期刊
CiteScore
1.80
自引率
10.00%
发文量
245
审稿时长
3 months
期刊介绍: Aims & Scope Letters in Drug Design & Discovery publishes letters, mini-reviews, highlights and guest edited thematic issues in all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis is on publishing quality papers very rapidly by taking full advantage of latest Internet technology for both submission and review of manuscripts. The online journal is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery.
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