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Synthesis, enzyme inhibitory kinetics, and computational studies of novel 1‐(2‐(4‐isobutylphenyl) propanoyl)‐3‐arylthioureas as Jack bean urease inhibitors
Author(s) -
Abdul Fattah Tanzeela,
Saeed Aamer,
Channar Pervaiz Ali,
Ashraf Zaman,
Abbas Qamar,
Hassan Mubashir,
Larik Fayaz Ali
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13090
Subject(s) - urease , chemistry , brine shrimp , enzyme kinetics , enzyme , kinetics , stereochemistry , docking (animal) , active site , nuclear chemistry , biochemistry , veterinary medicine , medicine , physics , quantum mechanics , traditional medicine
In this article, synthesis of a novel 1‐(2‐(4‐isobutylphenyl)propanoyl)‐3‐arylthioureas ( 4a–j) 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 4e, 4h, and 4j showed IC 50 values 0.0086 n m , 0.0081 n m , and 0.0094 n m , respectively. The enzyme inhibitory kinetics results showed that compound 4h inhibit the enzyme competitively while derivatives 4e and 4j are the mixed type inhibitors. The compound 4h reversibly binds the urease enzyme showing K i value 0.0012 n m . The K i values for 4e and 4j are 0.0025 n m and 0.003 n m , respectively. The antioxidant activity results reflected that compounds 4b, 4i, and 4j 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 4h may act as a lead candidate to design the clinically useful urease inhibitors.