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Design and synthesis of potent and selective β- glucuronidase inhibitor by virtual and in vitro screening

Author : Shazia Haider, Zafar Saied Saify, Mehrun-Nisa, Nousheen Mushtaq, Afshan Naz, Ajmal Khan, Bishnu P. Marasini, Seema Ashraf, Tabinda Z. M, Arshad Arain

Piperidine and pyrrolidine constitute an important fragment of biomolecules present in the naturally occurring compounds and they have shown potential biological activity. We have designed 4-(1-pyrrolidinyl) piperidine derivatives and virtually screened for β-glucuronidase by computational docking using Argus Lab followed by in vitro screening. Compounds were also screened for urease, phosphodiesterase and α- chymotrypsin inhibition to find selective inhibitor. Compound 2, 3, 4 have shown beta glucuronidase inhibition greater than standard D-Sacchric acid 1, 4 lactone (IC50 =48.4+1.25m). All the compounds were inactive for the other tested enzymes except compound 3 which exhibited weak urease inhibition. Compound 2, 4 and 6 can be used as selective β -glucuronidase inhibitor. Compound 2 {1-[2-(4′′-chloro-phenyl)-2-oxo-ethyl]- 4-pyrrolidin-1′-yl- piperidinium bromide} showed remarkable inhibition against -glucuronidase, with an IC50 value of 17.10 0.61 m, this is about three times more active than the standard drug.


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