Novel 1,3-diaryltriazene-substituted sulfaguanidine derivatives as selective carbonic anhydrase inhibitors: Synthesis, characterization, inhibition effects, and molecular docking studies

Abstract

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 the 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, the compounds may be potential alternative agents that can be used to treat or prevent diseases associated with glaucoma and hCA inhibition.