Abstract
Current research is based on biology-oriented synthesis of sulphadiazine derivatives and determination of their urease inhibitory activity. In this regard, a series of (E)-4-(benzylideneamino)-N-(pyrimidin-2-yl)benzenesulfonamide was synthesized from sulphadiazine and substituted aromatic aldehydes. The structures of synthesized compounds were ascertained by spectroscopic techniques, such as, FTIR, NMR and HRMS analysis, and in-vitro and in-silico investigation were carried out for the inhibition of urease. Ureases are harmful for humans by producing by-products of urea (ammonia and carbon dioxide). The most active compound (3l) against urease exhibited IC50 value of 2.21 ± 0.45 µM which is 10 times more potent than the standard thiourea (20.03 ± 2.06 µM). It is noteworthy that most of our synthesized compounds showed significant to excellent activities against urease enzyme and most of them substituted by halogen or hydroxy groups at ortho and para positions in their structures. Inhibition of enzyme by the synthesized analogues was in descending order as 3l > 3a > 3b > 3q > 3e > 3o > 3s > 3t > 3g > 3k > 3r > 3f > 3m > 3p > 3n > 3j > 3i > 3h. Moreover, molecular docking studies were performed to rationalize the binding interactions of the synthesized motifs with the active pocket of the urease enzyme. The synthesized sulphadiazine derivatives (3a–u) were found to be non-toxic, and presented passive gastrointestinal absorption.
Highlights
Current research is based on biology-oriented synthesis of sulphadiazine derivatives and determination of their urease inhibitory activity
Since there is no difference in the sequence for plants and bacteria from the available data and they both have the same active sites, Jack bean urease was marked as a prototype for characterization and studying the urease enzymes[4]
In search of more potent urease inhibitors, we have designed and synthesized Schiff ’s base derivatives of marketed drug sulphadiazine (1) by using wide range of aromatic aldehydes (2a–u) and subjected them to urease inhibition followed by molecular docking, ADME analysis and structure activity relationship (SAR) studies to discuss the varying effects of different incorporated functional groups
Summary
Current research is based on biology-oriented synthesis of sulphadiazine derivatives and determination of their urease inhibitory activity In this regard, a series of (E)-4-(benzylideneamino)N-(pyrimidin-2-yl)benzenesulfonamide was synthesized from sulphadiazine and substituted aromatic aldehydes. We determined inhibition of Jack b ean’s urease by various (E)-4(benzylideneamino)-N-(pyrimidin-2-yl)benzenesulfonamide (Schiff ’s base derivatives of sulphadiazine) These moieties have a relation with a large group of sulfonamide derivatives and formed by the condensation of sulphadiazine with substituted aromatic aldehdyes. In search of more potent urease inhibitors, we have designed and synthesized Schiff ’s base derivatives of marketed drug sulphadiazine (1) by using wide range of aromatic aldehydes (2a–u) and subjected them to urease inhibition followed by molecular docking, ADME analysis and structure activity relationship (SAR) studies to discuss the varying effects of different incorporated functional groups. To the best of our knowledge, except compounds 3a, 3b, 3c, 3e, 3f, 3g, 3h, 3q and 3t all synthesized compounds are new (Fig. 1)
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