DESIGN, SYNTHESIS, CHARACTERIZATION, BIOACTIVITY AND MOLECULAR DOCKING STUDIES OF NOVEL SULFAMIDES

Abstract

Starting from commercially available 4-phenylbutanoic acids, a series of novel sulfamides were synthesized and investigated for their inhibition properties on the human carbonic anhydrase I and II (hCA I and II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. SAR was also evaluated with molecular docking study. These new compounds were tested against hCA I and hCA II, BChE, and AChE. The majority of the synthetic compounds were more effective against AChE than tacrine, a common inhibitor. Additionally, tacrine was not the only synthetic substance that was more effective against BChE. The obtained results revealed that N,N-dimethyl-[3-(2,4-dimethoxyphenyl)propyl]sulfamide 25, with K_i of 94.22±42.37 nM against AChE and K_i of 230.91±46.22 nM against BChE, was the most potent compound against cholinesterase enzymes. These recently created substances were tested for their ability to inhibit hCA I and II isoforms. In comparison to the conventional inhibitor acetazolamide, the majority of produced sulfamide derivatives 25–29 also inhibited these investigated isoforms. In particular, sulfamide derivatives 25-29 with substituents N,N-dimethyl-[3-(3,5-dimethoxyphenyl)propyl]sulfamide 26 and N,N-dimethyl-[3-(3,4-dimethoxyphenyl)propyl]sulfamide 27 emerged as the most potent hCA inhibitors.