Abstract：
Sulfonamide compounds known as human carbonic anhydrase (hCA) inhibitors are used in the treatment of many diseases such as epilepsy, antibacterial, glaucoma, various diseases. 1,3-diaryl-substituted triazenes and sulfaguanidine are used for therapeutic purposes in many drug structures. Based on these two groups, the synthesis of new compounds is important. In the present study, the novel 1,3-diaryltriazene-substituted sulfaguanidine derivatives (SG1-13) were synthesized and fully characterized by spectroscopic and analytic methods. Inhibitory effect of these compounds on the hCA I and hCA II was screened as in vitro. All the series of synthesized compounds have been identified as potential hCA isoenzymes inhibitory with KI values in the range of 6.44±0.74-86.85±7.01 nM for hCA I and with KI values in the range of 8.16±0.40-77.29±9.56 nM for hCA II. Moreover, the new series of compounds showed a more effective inhibition effect than the acetazolamide used as a reference. The possible binding positions of the compounds with a binding affinity to the hCA I and hCA II was demonstrated by in silico studies. In conclusion, compounds with varying degrees of affinity for hCA isoenzymes have been designed and as selective hCA inhibitors. These compounds may be potential alternative agents that can be used to treat or prevent diseases associated with glaucoma and hCA inhibition.
摘要：
磺酰胺化合物被称为人类碳酸酐酶（hCA）抑制剂，用于治疗许多疾病，例如癫痫，抗菌，青光眼,各种疾病。1,3-二芳基取代的三氮烯和磺胺胍在许多药物结构中用于治疗目的。基于这两组，新化合物的合成很重要。在本研究中,合成了新型的1,3-二芳基三氮烯取代的磺胺胍衍生物（SG1-13），并通过光谱和分析方法对其进行了充分表征。在体外筛选这些化合物对hCAI和hCAII的抑制作用。所有合成的化合物系列均已被鉴定为潜在的hCA同工酶抑制作用，hCAI的KI值在6.44±0.74-86.85±7.01nM的范围内，而hCAII的KI值在8.16±0.40-77.29±9.56nM的范围内。此外，与用作参考的乙酰唑胺相比，新系列化合物显示出更有效的抑制作用。通过计算机模拟研究证明了对hCAI和hCAII具有结合亲和力的化合物的可能结合位置。总之,已经设计了对hCA同工酶具有不同程度亲和力的化合物，并将其用作选择性hCA抑制剂。这些化合物可以是可用于治疗或预防与青光眼和hCA抑制相关的疾病的潜在替代药剂。
