2-苯基苯并咪唑新型1,2,3-三唑衍生物的合成、表征、ADME研究及抗菌评价。

Asmaa Adnan Abdulnabi, Karima Fadhil Ali, Basma M.Abd Razik
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摘要

合成了含有酰胺、叠氮化物和1,2,3-三唑的新型2-氨基苯并咪唑衍生物。以邻苯二胺和对氨基苯甲酸为原料,合成了化合物3。用氯乙酰氯将化合物3转化为酰胺,得到化合物4。将化合物4与叠氮化钠化合成一个叠氮化基团的化合物。化合物5经乙炔衍生物处理后转化为1,2,3-三唑衍生物。FTIR, 1H-NMR和质谱已被用来确认各种物质的化学结构。利用孔扩散琼脂技术,对最终产物进行体外检测,预测其对两种革兰氏阳性菌和两种革兰氏阴性菌的活性以及对白色念珠菌的抗真菌活性。与甲氧苄啶和氟康唑作为对照抗菌和抗真菌药物相比,所有终产物均表现出中等至强效的活性。还使用瑞士ADME进行ADME测试,以确定合成分子的生物利用度、药物相似性和拓扑极性表面积。结果表明,所测化学物质均可经口吸收,并符合利宾斯基规律。
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Synthesis, Characterization, ADME Study and Antimicrobial Evaluation of New 1,2,3-triazole Derivatives of 2-phenyl benzimidazole.
Novel 2-amino benzimidazole derivatives containing amide, azide and 1,2,3-triazole moieties have been synthesized. Compound 3 was synthesized by reaction of o-phenylenediamine with p-aminobenzoic acid. Compound 3 was converted into amide by treatment with chloroacetyl chloride to get compound 4. Compound 4 and sodium azide were combined to create compound which has an azide group. Compound 5 was converted into 1,2,3-triazole derivatives by treatment with acetylene derivatives. FTIR, 1H-NMR, and Mass spectra have been used to confirm the chemical structures of various substances. By using a technique called well diffusion agar, the final products were examined in vitro to predict activity against two kinds of gram-positive bacteria and two kinds of gram-negative bacteria as well as the antifungal activity against Candida albicans fungus. All the final products exhibited moderate to potent activity compared to Trimethoprim and Fluconazole as reference antibacterial and antifungal drugs respectively. Swiss ADME was also used to undertake ADME tests to determine the bioavailability, drug-likeness and topological polar surface area of the synthesized molecule. The results showed that every chemical tested was absorbed orally and followed the Lipinski rule.
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