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Development of sulfonamide-based Schiff bases targeting urease inhibition: Synthesis, characterization, inhibitory activity assessment, molecular docking and ADME studies

Research output: Contribution to journalArticle

Asad Hamad, Mohsin Khan, Miraz Rahman, Irshad Ahmad, Zaheer ul-Huq, Samra Khan, Zahid Shafiq

Original languageEnglish
Article number104057
Pages (from-to)1-8
Number of pages8
JournalBIOORGANIC CHEMISTRY
Volume102
DOIs
Published26 Jun 2020

King's Authors

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 [sbnd]OH groups gave IC 50 value of 2.20 µM for urease inhibition against the standard Thiourea (IC 50 = 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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