本研究采用尾靠法合成了一个由十二种β-内酰胺取代苯磺酰胺（5a-l）组成的文库。运用红外光谱（IR）、质子核磁共振（1H NMR）、碳十三核磁共振（13C NMR）和元素分析技术对合成的化合物进行了表征。对这些新合成的化合物在体外对二种碳酸酐酶（hCA）的活性和乙酰胆碱酯酶（AChE）的抑制能力进行了测试。结果显示合成的化合物是hCA I的有效抑制剂，其KI值在低纳摩尔范围内（66.60-278.40 nM），相较之下，参比药物乙酰唑胺（AAZ）的KI值为439.17 nM。化合物5a、5d-g和5l对hCA II产生了有效的抑制作用，其KI值分别为69.56, 39.64, 79.63, 74.76, 78.93和74.94 nM（AAZ，KI值为98.28 nM）。值得注意的是，化合物5a对hCA II表现出选择性抑制作用，选择性系数大于4倍。在对AChE的抑制方面，合成的化合物的KI值范围为30.95-154.50 nM，而参比药物他克林的KI值为159.61 nM。同时，对化合物5f、5h和5l进行了抑制MCF-7癌细胞系增殖的评估，发现其具有潜在的抗癌活性，且比5-氟尿嘧啶和顺铂更具潜力。分子对接研究表明这些化合物的磺胺基团与hCA的活性位点紧密结合并与Zn2+离子相互作用。此外，通过进行200 ns的分子动力学模拟评估了每个酶-配体复合物的稳定性和动力学。还基于ADME/T结果估计了化合物是否符合Lipinski和Jorgensen规则。这些结果显示合成的分子有潜力成为有效和安全的hCA和AChE抑制剂，并且可以作为领先药物。由Ramaswamy H. Sarma传递。

In this study, a library of twelve beta-lactam-substituted benzenesulfonamides (5a-l) was synthesized using the tail-approach method. The compounds were characterized using IR, 1H NMR, 13C NMR and elemental analysis techniques. These newly synthesized compounds were tested for their ability to inhibit the activity of two carbonic anhydrases (hCA) isoforms, I and II, and acetylcholinesterase (AChE) in vitro. The results showed that the synthesized compounds were potent inhibitors of hCA I, with KIs in the low nanomolar range (66.60-278.40 nM) than the reference drug acetazolamide (AAZ), which had a KI of 439.17 nM. The hCA II was potently inhibited by compounds 5a, 5d-g and 5l, with KIs of 69.56, 39.64, 79.63, 74.76, 78.93 and 74.94 nM, respectively (AAZ, KI of 98.28 nM). Notably, compound 5a selectively inhibited hCA II with a selectivity of > 4-fold over hCA I. In terms of inhibition of AChE, the synthesized compounds had KIs ranging from 30.95 to 154.50 nM, compared to the reference drug tacrine, which had a KI of 159.61 nM. Compounds 5f, 5h and 5l were also evaluated for their ability to inhibit the MCF-7 cancer cell line proliferation and were found to have promising anticancer activity, more potent than 5-fluorouracil and cisplatin. Molecular docking studies suggested that the sulfonamide moiety of these compounds fits snugly into the active sites of hCAs and interacts with the Zn2+ ion. Furthermore, molecular dynamics simulations were performed for 200 ns to assess the stability and dynamics of each enzyme-ligand complex. The acceptability of the compounds based on Lipinski's and Jorgensen's rules was also estimated from the ADME/T results. These results indicate that the synthesized molecules have the potential to be developed into effective and safe inhibitors of hCAs and AChE and could be lead agents.Communicated by Ramaswamy H. Sarma.