Bio-oriented synthesis of new sulphadiazine derivatives for urease inhibition and their pharmacokinetic analysis

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 aldehy...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Scientific reports Ročník 11; číslo 1; s. 18973 - 14
Hlavní autoři: Hamad, Asad, Khan, Mohsin Abbas, Ahmad, Irshad, Khalil, Ruqaiya, Khalid, Muhammad, Abbas, Urva, Azhar, Rahat, Uddin, Jalal, Batiha, Gaber El-Saber, Khan, Ajmal, Shafiq, Zahid, Al-Harrasi, Ahmed
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 23.09.2021
Nature Publishing Group
Nature Portfolio
Témata:
631/154
631/45
631/92
Aldehydes
Ammonia
Carbon dioxide
Chemistry, Pharmaceutical
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - pharmacology
Enzymes
Humanities and Social Sciences
Inhibitory Concentration 50
Molecular Docking Simulation
Molecular Structure
multidisciplinary
NMR
Nuclear magnetic resonance
Pharmacokinetics
Science
Science (multidisciplinary)
Structure-Activity Relationship
Sulfadiazine - analogs & derivatives
Sulfadiazine - chemical synthesis
Sulfadiazine - pharmacology
Urea
Urease
Urease - antagonists & inhibitors
ISSN:2045-2322, 2045-2322
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí: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 IC 50 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.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-98413-x