New functionalized acrylamide derivatives bearing sulfisoxazole moiety were designed to target bacterial dihydropteroate synthase (DHPS). The in vitro antimicrobial activities of these compounds were assessed. The E-configuration of compound 5b was proved by single crystal X-ray analysis. Compounds 5g and 5h displayed double the activity of ampicillin against B. subtilis. Also, 5h was two times more active than gentamycin against E. coli. Interestingly, compounds 5f-g, 7c, 8a, 8c exhibited two folds the potency of amphotericin B against S. racemosum while 5h displayed three folds the activity of amphotericin B against S. racemosum. Most of the synthesized compounds showed superior activities to the parent sulfisoxazole and were non-toxic to normal cells. DHPS is confirmed to be a putative target for our compounds via antagonizing their antibacterial activity by the folate precursor (p-aminobenzoic acid) and product (methionine) on E. coli ATCC 25922. Docking experiments against DHPS rationalized the observed antibacterial activity. Additionally, compound 5g was evaluated as a selective targeting vector for ^99mTc that showed a remarkable uptake and targeting ability towards the infection site that was induced in mice.

设计新的带有磺基异恶唑部分的官能化丙烯酰胺衍生物，以靶向细菌二氢蝶呤合酶（DHPS）。在体外，这些化合物的抗微生物活性进行了评估。通过单晶X射线分析证明了化合物5b的E-构型。化合物5g和5h显示出氨苄青霉素对枯草芽孢杆菌的两倍活性。同样，5h的抗大肠杆菌活性比庆大霉素高两倍。有趣的是，化合物5f-g，7c，8a，8c表现出的两性霉素B抗药性是其的两倍。消旋葡萄球菌在5h时显示出两性霉素B对消旋葡萄球菌的活性的三倍。大多数合成的化合物显示出优于母体磺异恶唑的活性，并且对正常细胞无毒。通过在大肠杆菌ATCC 25922上通过叶酸前体（对氨基苯甲酸）和产物（蛋氨酸）拮抗其抗菌活性，证实DHPS是我们化合物的推定目标。针对DHPS的对接实验使观察到的抗菌活性合理化。此外，化合物5g被评估为^99m的选择性靶向载体Tc对小鼠诱导的感染部位具有显着的摄取和靶向能力。