Sulfonamide-phosphonate hybrids as new carbonic anhydrase inhibitors: In vitro enzymatic inhibition, molecular modeling, and ADMET prediction

摘要: In the presented work, we report the synthesis of a new series of sulfonamide-phosphonate hybrids 4a-m. These newly synthesized compounds were assessed for their inhibitory effects toward two human carbonic anhydrase isoforms I and II (hCA I and II). These examined isoforms were as well inhibited by the most of prepared sulfonamide-phosphonates in comparison to standard inhibitor acetazolamide. Obtained data exhibited that compounds 4b-m with Ki values in the range of 8.11–48.08 nM were more potent than standard drug acetazolamide with Ki value of 64.52 Nm against hCA I. Moreover, all the synthesized compounds (Ki values = 7.08–64.24 nM), with the exception of compound 4b, were more potent than acetazolamide (Ki value = 75.36) against hCA II. In particular, sulfonamide-phosphonates 4l and 4j, respectively, with substituents 5‑chloro-2-nitro and 2,3-dichloro emerged as the most potent hCA …