The superbug infection caused by metallo-β-lactamases (MβLs) carrying drug-resistant bacteria, specifically, New Delhi metallo-β-lactamase (NDM-1) has become an emerging threat. In an effort to develop novel inhibitors of NDM-1, thirteen thiosemicarbazones (1a-1m) were synthesized and assayed. The obtained molecules specifically inhibited NDM-1, with an IC₅₀ in the range of 0.88–20.2 µM, and 1a and 1f were found to be the potent inhibitors (IC₅₀ = 1.79 and 0.88 μM) using cefazolin as substrate. ITC and kinetic assays indicated that 1a irreversibly and non-competitively inhibited NDM-1 in vitro. Importantly, MIC assays revealed that these molecules by themselves can sterilize NDM-producing clinical isolates EC01 and EC08, exhibited 78-312-fold stronger activities than the cefazolin. MIC assays suggest that 1a (16 μg ml⁻¹) has synergistic antimicrobial effect with ampicillin, cefazolin and meropenem on E. coli producing NDM-1, resulting in MICs of 4-32-, 4-32-, and 4-8-fold decrease, respectively. These studies indicate that the thiosemicarbazide is a valuable scaffold for the development of inhibitors of NDM-1 and NDM-1 carrying drug-resistant bacteria.

由携带耐药菌的金属-β-内酰胺酶（MβLs）引起的超级细菌感染，特别是新德里金属-β-内酰胺酶（NDM-1）已成为一种新兴威胁。为了开发新的 NDM-1 抑制剂，合成并分析了13 种缩氨基硫脲 ( 1a - 1m )。获得的分子特异性抑制 NDM-1，IC ₅₀在 0.88–20.2 µM 范围内，并且发现1a和1f是 使用头孢唑啉作为底物的有效抑制剂（IC ₅₀ = 1.79 和 0.88 µM）。ITC 和动力学分析表明1a在体外不可逆地和非竞争性地抑制 NDM-1。重要的是，MIC 测定表明这些分子本身可以对产生 NDM 的临床分离株 EC01 和 EC08 进行消毒，表现出比头孢唑啉强 78-312 倍的活性。MIC 测定表明1a (16 μg ml ^-1 ) 与氨苄青霉素、头孢唑啉和美罗培南对产生 NDM-1 的大肠杆菌具有协同抗菌作用，导致 MIC 为 4-32-、4-32- 和 4-8-倍减少，分别。这些研究表明氨基硫脲是开发 NDM-1 和 NDM-1 携带耐药细菌抑制剂的有价值的支架。