Synthesis, in vitro urease inhibitory potential and molecular docking study of benzofuran-based-thiazoldinone analogues (original) (raw)

in continuation of our work on enzyme inhibition, the benzofuran-based-thiazoldinone analogues (1-14) were synthesized, characterized by HREI-MS, 1 H and 13 cnMR and evaluated for urease inhibition. Compounds 1-14 exhibited a varying degree of urease inhibitory activity with IC 50 values between 1.2 ± 0.01 to 23.50 ± 0.70 µM when compared with standard drug thiourea having IC 50 value 21.40 ± 0.21 µM. Compound 1, 3, 5 and 8 showed significant inhibitory effects with IC 50 values 1.2 ± 0.01, 2.20 ± 0.01, 1.40 ± 0.01 and 2.90 ± 0.01 µM respectively, better than the rest of the series. A structure activity relationship (SAR) of this series has been established based on electronic effects and position of different substituents present on phenyl ring. Molecular docking studies were performed to understand the binding interaction of the compounds. Benzofuran scaffolds due to its profound chemotherapeutic, physiological properties and their dynamic nature has attracted the attention of chemist during last few years 1. Acting as versatile scaffolds, benzofuran derivatives can be used to synthesize potentially new therapeutic agents 2. These scaffolds exhibited biological properties such as antimicrobial 3 , analgesic 4 , anti-hyperglycemic 5 , anti-parasitic 6 , antitumor and kinase inhibitors 7. Besides these properties benzofuran scaffolds also found application as oxidant 8 , fluorescent sensor 9 , brightening agent, antioxidant and in other field of chemistry and agriculture 10. Urease is a metalloenzyme contain nickel that is responsible for catalyzing urea hydrolysis to ammonia and carbamate, the latter spontaneously hydrolyzing to carbonic acid and a second molecule of ammonia in an uncatalyzed reaction 11. Ammonia molecules thus formed are protonated by water at physiological pH, whereas the carbonic acid dissociates and causes an increase in pH.