Urease enzyme is a virulence factor that helps in colonization and maintenance of highly pathogenic bacteria in human. Hence, the inhibition of urease enzymes is well-established to be a promising approach for preventing deleterious effects of ureolytic bacterial infections. In this work, novel thiobarbiturate derivatives were synthesized and evaluated for their urease inhibitory activity. All tested compounds effectively inhibited the activity of urease enzyme. Compounds 1, 2a, 2b, 4 and 9 displayed remarkable anti-urease activity (IC₅₀ = 8.21–16.95 μM) superior to that of thiourea reference standard (IC₅₀ = 20.04 μM). Moreover, compounds 3a, 3g, 5 and 8 were equipotent to thiourea. Among the tested compounds, morpholine derivative 4 (IC₅₀ = 8.21 µM) was the most potent one, showing 2.5 folds the activity of thiourea. In addition, the antibacterial activity of the synthesized compounds was estimated against both standard strains and clinical isolates of urease producing bacteria. Compound 4 explored the highest potency exceeding that of cephalexin reference drug. Moreover, biodistribution study using radiolabeling approach revealed a remarked uptake of ^99mTc-compound 4 into infection induced in mice. Furthermore, a molecular docking analysis revealed proper orientation of title compounds into the urease active site rationalizing their potent anti-urease activity.

脲酶是一种致病因子，有助于人类中高致病菌的定殖和维持。因此，已经充分确定了脲酶的抑制作用，这是防止尿素分解细菌感染的有害作用的有前途的方法。在这项工作中，合成了新的硫代巴比妥酸酯衍生物，并评估了其脲酶抑制活性。所有测试的化合物均有效抑制脲酶的活性。化合物1、2a，2b，4和9表现出显着的抗脲酶活性（IC ₅₀  = 8.21–16.95μM），优于硫脲参考标准品（IC ₅₀  = 20.04μM）。此外，化合物3a，3g，5和8与硫脲等价。在测试的化合物中，吗啉衍生物4（IC ₅₀  = 8.21 µM）是最有效的化合物，其硫脲活性为2.5倍。另外，估计了合成化合物对产生尿素酶的标准菌株和临床分离株的抗菌活性。化合物4探索了超过头孢氨苄参考药物的最高效价。此外，使用放射标记方法的生物分布研究表明，小鼠诱发的感染明显吸收了^99m Tc化合物4。此外，分子对接分析显示标题化合物正确进入尿素酶活性位点，使其有效的抗脲酶活性合理化。