含膦酸酯结构单元的磺胺衍生物合成与抗菌活性

Synthesis and Antibacterial Activity of Sulfanilamide Derivatives Con-taining Phosphonate Moiety

摘要:

为了寻找抗菌候选化合物，采用基于片段的药物发现方法，以中间体氨基膦酸酯和磺酰氯为原料，设计合成了15个含膦酸酯结构单元的磺胺衍生物，经IR、1HNMR和13CNMR确认结构。采用两倍稀释法测定目标化合物的MIC（最小抑菌浓度）。结果表明：部分目标化合物呈潜在的抗菌活性，对所测试标准菌和耐药菌均有抑制活性。其中化合物Ⅱf〔N-[（二乙氧基膦酰基）-4-氟苯甲基]-4-甲氧基苯磺酰胺〕对金黄色葡萄球菌（S. aureus）、大肠埃希菌（E. coli）、耐甲氧西林金黄色葡萄球菌（MRSA）及耐氟喹诺酮类大肠杆菌（MREC）的MIC分别为32、64、128和128 μg/mL，化合物Ⅱl〔N-[（二乙氧基膦酰基）-4-氟苯甲基]-4-甲基苯磺酰胺〕对S. aureus、E. coli、MRSA及MREC的MIC分别为32、32、64和64μg/mL，抗菌活性优于对照药磺胺嘧啶（对S. aureus和E. coli的MIC为512μg/mL，对耐药菌无活性）。

Abstract:

In order to find antibacterial candidate agents. Using fragment based drug discovery methods, fifteen sulfanilamide derivatives were designed and synthesized with aminophosphonate and sulfonyl chloride as raw material. Their structures were confirmed by IR, 1HNMR and 13CNMR. MICs of the target compounds were determined by double dilution method. The results showed that some compounds have potential inhibitory activities against standard bacteria and drug resistant bacteria, the MIC of the compoundⅡf〔N-[（diethoxyphosphonyl -4-fluorobenzyl]-4-methoxybenzenesulfonamide〕 for S.aureus, E. coli, MRSA and MREC was 32, 64, 128, 128μg/mL, respectively, and the MIC of the compoundⅡl 〔N-[（diethoxyphosphonyl -4-fluorobenzyl]-4-fluorobenzenesulfonamide〕was 32, 32, 64, 64μg/mL, respectively. Its antibacterial activities were better than that of the control drug sulfadiazine.