Synthesis and urease inhibitory activity of 1,4-benzodioxane-based thiosemicarbazones: Biochemical and computational approach
2020; Elsevier BV; Volume: 1209; Linguagem: Inglês
10.1016/j.molstruc.2020.127922
ISSN1872-8014
AutoresMuhammad Tariq Shehzad, Ajmal Khan, Muhammad Islam, Abdul Hameed, Mohammed Khiat, Sobia Ahsan Halim, Muhammad U. Anwar, Syed Raza Shah, Javid Hussain, René Csük, Samra Khan, Ahmed Al‐Harrasi, Zahid Shafiq,
Tópico(s)Enzyme function and inhibition
ResumoThe hyperactivity of urease enzyme is associated with clinically important complications including stomach ulcers and kidney stones. This enzyme provides a suitable environment to Helicobacter pylori at low pH in the stomach, a causative agent of peptic and ulcer gastric that may lead to cancer. Natural and synthetic small molecules were reported to inhibit urease enzyme. Within this context, a new series of 1,4-benzodioxane-based thiosemicarbazones (3a-p) were synthesized and screened in vitro against urease enzyme to elucidate their anti-urease activity. All the compounds displayed potent inhibitory potential with IC50 values ranging between 3.65 ± 2.64 to 31.9 ± 1.094 μM, under positive control of thiourea (IC50 = 20.8 ± 0.75 μM). Structural activity relationship (SAR) has revealed a variation based on substituents pattern at R group. The results of docking study suggest that these compounds thermodynamically binds via nickel atoms present in the active-site of urease. The in silico docking analysis and our experimental findings are in excellent co-relation. The pharmacokinetic behavior of all the compounds were also predicted.
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