Development of sulfonamide-based Schiff bases targeting urease inhibition: Synthesis, characterization, inhibitory
Asad Hamad1, Mohsin Abbas Khan1, Khondaker Miraz Rahman2
1Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.
Abstract:
A series of Sulfonamide-based Schiff bases (E)-4-(benzylideneamino)-N-(6-methoxypyridazin-3-yl) benzenesulfonamide (3a-r) targeting Urease Inhibition was synthesized from sulphamethoxy pyridazine and substituted aldehydes. The prepared compounds were characterized by various spectroscopic techniques including FTIR, 1HNMR, 13CNMR, and spectrometric HRMS analysis. The most active agent (3g) bearing halogens and OH groups gave IC50 value of 2.20 µM for urease inhibition against the standard Thiourea (IC50 = 20.03 ± 2.06) and the overall trend within the series was 3g > 3n > 3p > 3j > 3q > 3h, 3o > 3l, 3r > 3k, 3m > 3a > 3d > 3e > 3f. Structure-activity relationship study established that the nature as well as the position of varying groups attached to aryl group had crucial roles in defining the urease inhibition activity. Additionally, in silico investigation was carried out which demonstrated that the compounds exhibit polar and apolar contacts with the crucial residues in the binding site of urease. The ADME analysis suggested all the synthesized compounds to be non-toxic, and likely to undergo passive gastrointestinal absorption. Taken together, the study suggests that the synthesized Sulfonamide-based Schiff bases derivatives may serve as potential hits as urease inhibitors.
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