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- Title
Synthesis, enzyme inhibitory kinetics, and computational studies of novel 1‐(2‐(4‐isobutylphenyl) propanoyl)‐3‐arylthioureas as Jack bean urease inhibitors.
- Authors
Abdul Fattah, Tanzeela; Saeed, Aamer; Channar, Pervaiz Ali; Larik, Fayaz Ali; Ashraf, Zaman; Abbas, Qamar; Hassan, Mubashir
- Abstract
In this article, synthesis of a novel 1‐(2‐(4‐isobutylphenyl)propanoyl)‐3‐arylthioureas (<bold>4a–j)</bold> as jack bean urease inhibitors has been described. Freshly prepared 2‐(4‐isobutylphenyl) propanoyl isothiocyanate was treated with substituted aromatic anilines in one pot using anhydrous acetone. The compounds <bold>4e, 4h,</bold> and <bold>4j</bold> showed IC50 values 0.0086 n m, 0.0081 n m, and 0.0094 n m, respectively. The enzyme inhibitory kinetics results showed that compound <bold>4h</bold> inhibit the enzyme competitively while derivatives <bold>4e</bold> and <bold>4j</bold> are the mixed type inhibitors. The compound <bold>4h</bold> reversibly binds the urease enzyme showing K<italic>i</italic> value 0.0012 n m. The K<italic>i</italic> values for <bold>4e</bold> and <bold>4j</bold> are 0.0025 n m and 0.003 n m, respectively. The antioxidant activity results reflected that compounds <bold>4b, 4i,</bold> and <bold>4j</bold> showed excellent radical scavenging activity. Moreover, the cytotoxic activity of the target compounds was evaluated using brine shrimp assay and it was found that all of the synthesized compounds exhibited no cytotoxic effects to brine shrimps. The computational molecular docking and molecular dynamic simulation of title compounds were also performed, and results showed that the wet laboratory findings are in good agreement to the dry laboratory results. Based upon our results, it is proposed that compound <bold>4h</bold> may act as a lead candidate to design the clinically useful urease inhibitors.
- Subjects
ENZYME inhibitors; UREASE; ISOTHIOCYANATES; MOLECULAR docking; SHRIMPS
- Publication
Chemical Biology & Drug Design, 2018, Vol 91, Issue 2, p434
- ISSN
1747-0277
- Publication type
Article
- DOI
10.1111/cbdd.13090