Synthesis, in silico and in vitro antimicrobial efficacy of some amidoxime-based benzimidazole and benzimidamide derivatives.

IF 4.1 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Gbolahan O Oduselu, Olayinka O Ajani, Temitope A Ogunnupebi, Oluwadunni F Elebiju, Damilola S Bodun, Oluwabukayo Toluwunmiju Opebiyi, Ezekiel Adebiyi
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引用次数: 0

Abstract

Amidoximes are employed as building blocks to synthesise heterocyclic motifs with biological significance. They are very reactive and are used as prodrugs of amidine. This present study unveils the synthesis of amidoxime-based benzimidazole and benzimidamide motifs and evaluates their in silico and in vitro antimicrobial potential as future drug candidates. The compounds (2a, 2b, 4a-c) were synthesized using multi-step synthetic pathways. The synthesised compounds were characterised using physico-chemical examination, 1H- and 13C-NMR, DEPT-135, and FT-IR spectroscopic analyses. The in silico antimicrobial potentials of the synthesized compounds were carried out against glucosamine-6-phosphate synthase of E. coli (PDB ID: 2VF5), and N-myristoyltransferase (NMT) of C. albicans (PDB ID: 1IYL), while the in vitro antimicrobial screening was investigated against selected bacteria and fungi. The in silico studies were carried out using predicted ADMET screening, molecular docking, MM-GBSA, induced-fit docking (IFD), and molecular dynamics (MD) simulation studies. Furthermore, the in vitro experimental validations were performed using the agar diffusion method and the standard antibacterial and antifungal drugs used were gentamicin and ketoconazole respectively. The predicted toxicity test of the compounds showed no significant risk, except for 4c, which showed high tumorigenic risk. Compounds 2b and 2a gave better binding energies; -8.0 kcal mol-1 for 2VF5 and -11.7 kcal mol-1 for 1IYL, respectively. The antimicrobial zone of inhibition and minimum inhibitory concentration values were 40 mm and 3.90 mg mL-1 against S. mutans, then 42 mm and 1.90 mg mL-1 against C. albicans. Potential antimicrobial drug candidates have been identified in this report and should be explored for future preclinical research.

偕胺肟基苯并咪唑及苯并咪酰胺衍生物的合成、硅法及体外抗菌效果研究。
偕胺肟被用作合成具有生物学意义的杂环基序的基石。它们具有很强的活性,被用作脒的前药。本研究揭示了偕胺肟基苯并咪唑和苯并咪酰胺基序的合成,并评估了它们作为未来候选药物的硅和体外抗菌潜力。化合物(2a, 2b, 4a-c)通过多步合成途径合成。合成的化合物通过物理化学检查,1H-和13C-NMR, DEPT-135和FT-IR光谱分析进行了表征。合成的化合物对大肠杆菌(PDB ID: 2VF5)和白色念珠菌(PDB ID: 1IYL)的氨基葡萄糖-6-磷酸合成酶(glucosamine-6-phosphate synthase, PDB ID: 2VF5)和n -肉豆烯酰基转移酶(N-myristoyltransferase, NMT)进行了硅内抗菌电位测定,并对选定的细菌和真菌进行了体外抗菌筛选。通过预测ADMET筛选、分子对接、MM-GBSA、诱导配合对接(IFD)和分子动力学(MD)模拟研究进行了计算机研究。采用琼脂扩散法进行体外实验验证,标准抗菌药物为庆大霉素,标准抗真菌药物为酮康唑。除4c具有较高的致瘤风险外,其余化合物的预测毒性试验均无显著风险。化合物2b和2a具有较好的结合能;2VF5为-8.0 kcal mol-1, 1IYL为-11.7 kcal mol-1。对变形链球菌的抑菌区和最小抑菌浓度分别为40 mm和3.90 mg mL-1,对白色念珠菌的抑菌区分别为42 mm和1.90 mg mL-1。本报告已确定了潜在的候选抗菌药物,并应在未来的临床前研究中进行探索。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
5.80
自引率
2.40%
发文量
129
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