Presently available chemical based synthetic preservative have emerged with various side effects, so the aspiration of natural and side effect free novel preservative has been greatly increased. As the natural preservative exhibit poor side effect with improved preservative efficacy. The recent development in computational studies leads advancement in drug designing and discovery of novel glucosamine-6-phosphate synthase (G-6-P synthase) inhibition based natural antimicrobial preservatives. Here, selected aesculin derivatives were screened for G-6-P synthase inhibition via docking study and evaluated for antioxidant, antimicrobial, preservative efficacy as well stability study. Modified aesculin derivatives were designed, synthesized and showed potent G-6-P synthase inhibition with remarkable antimicrobial, antioxidant, preservative efficacy and stability study. The molecular docking with target pdb id 1moq from G-6-P synthase resulted with better dock score and energy for compound 1 as compared to standard drugs streptomycin, ciprofloxacin, ampicillin and fluconazole, that supported the wet lab results. Among the synthesized compounds, the compound 1 possessed good antioxidant activity as compared to standard L-ascorbic acid. The resultant data for antimicrobial activity of aesculin derivatives revealed compound 1 as the most potent antimicrobial compound as compared to the standard drugs streptomycin, ciprofloxacin, ampicillin and fluconazole. While compound 2 showed better antimicrobial activity as compared to streptomycin, ciprofloxacin, ampicillin. The preservative efficacy test for compound 1 in aloe vera juice and white lotion USP has been showed the log CFU/mL values within the prescribed limit of USP standard and results were comparable to standard sodium benzoate, ethyl paraben and propyl paraben. Compound 1 has been found to be within prescribed limit of stability study over six month. Compound 1 showed the potent G-6-P synthase inhibitory, antioxidant, antimicrobial, preservative efficacy and stability study results as compared to standard drugs taken. The results have found comparable to molecular docking results, and this final compound may be used as new preservatives for food and pharmaceutical products. Moreover, the mechanistic insight into the docking poses was also explored by binding interactions of aesculin derivatives inside the pdb id 1moq. These results also supported the results for novel synthesized G-6-P synthase inhibitors.

中文翻译：

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基于七叶苷的葡糖胺-6-磷酸合酶抑制剂作为食品和药品的新型防腐剂：计算机研究、抗氧化、抗菌和防腐剂功效评估

目前可用的化学合成防腐剂已经出现了各种副作用，因此大大增加了对天然无副作用的新型防腐剂的渴望。由于天然防腐剂副作用小，防腐效果更好。计算研究的最新进展推动了药物设计的进步，并推动了基于天然抗菌防腐剂的新型氨基葡萄糖-6-磷酸合酶（G-6-P 合酶）抑制的发现。在这里，通过对接研究筛选了选定的七叶苷衍生物的 G-6-P 合酶抑制作用，并评估了抗氧化、抗菌、防腐功效以及稳定性研究。设计、合成了修饰的七叶苷衍生物，并显示出有效的 G-6-P 合酶抑制作用，具有显着的抗菌、抗氧化、防腐效力和稳定性研究。与标准药物链霉素、环丙沙星、氨苄西林和氟康唑相比，与来自 G-6-P 合酶的目标 pdb id 1moq 的分子对接导致化合物 1 的对接评分和能量更好，这支持湿实验室结果。在合成的化合物中，与标准L-抗坏血酸相比，化合物1具有良好的抗氧化活性。七叶树素衍生物抗微生物活性的所得数据表明，与标准药物链霉素、环丙沙星、氨苄西林和氟康唑相比，化合物 1 是最有效的抗微生物化合物。与链霉素、环丙沙星、氨苄青霉素相比，化合物 2 显示出更好的抗菌活性。化合物 1 在芦荟汁和白洗液 USP 中的防腐效力测试显示 log CFU/mL 值在 USP 标准规定的限度内，结果与标准苯甲酸钠、对羟基苯甲酸乙酯和对羟基苯甲酸丙酯相当。已发现化合物 1 在六个月的稳定性研究中处于规定的限度内。与服用的标准药物相比，化合物 1 显示出有效的 G-6-P 合酶抑制、抗氧化、抗微生物、防腐功效和稳定性研究结果。结果发现与分子对接结果相当，这种最终化合物可能用作食品和药品的新型防腐剂。此外，还通过 pdb id 1moq 内七叶树素衍生物的结合相互作用探索了对对接姿势的机械洞察。