Synthesis, Molecular Docking and β-Glucuronidase Inhibitory Potential of Indole Base Oxadiazole Derivatives
Abstractβ-glucuronidase is a lysosomal glycosidase enzyme which catalyzes the extracellular matrix of cancer and normal cells and the glycosaminoglycans of the cell membrane, which is important for cancer cell proliferation, invasion, and metastasis. Liver cancer, colon carcinoma, and neoplasm bladder are triggered by the increase of the level of β-glucuronidase activity. The most valuable structures are indole and oxadiazole which has gain immense attention because of its pharmacological behavior and display many biological properties. Twenty-two (1–22) analogs of indole based oxadiazole were synthesized and screened for their inhibitory potential against β-glucuronidase. Majority of the compounds showed potent inhibitory potential with IC50 values ranging between 0.9 ± 0.01 to 46.4 ± 0.9 µM, under positive control of standard drug d-saccharic acid 1,4 lactone (IC50 = 48.1 ± 1.2 µM). Structural activity relationship (SAR) has been established for all synthesized compounds. To shed light on molecular interactions between the synthesized compounds and β-glucuronidase, 1, 4, and 6 compounds were docked into the active binding site of β-glucuronidase. The obtained results showed that this binding is thermodynamically favorable and β-glucuronidase inhibition of the selected compounds increases with the number of hydrogen bonding established in selected compound-β-glucuronidase complexes. View Full-Text
Share & Cite This Article
Anouar, E.H.; Moustapha, M.E.; Taha, M.; Geesi, M.H.; Farag, Z.R.; Rahim, F.; Almandil, N.B.; Farooq, R.K.; Nawaz, M.; Mosaddik, A. Synthesis, Molecular Docking and β-Glucuronidase Inhibitory Potential of Indole Base Oxadiazole Derivatives. Molecules 2019, 24, 963.
Anouar EH, Moustapha ME, Taha M, Geesi MH, Farag ZR, Rahim F, Almandil NB, Farooq RK, Nawaz M, Mosaddik A. Synthesis, Molecular Docking and β-Glucuronidase Inhibitory Potential of Indole Base Oxadiazole Derivatives. Molecules. 2019; 24(5):963.Chicago/Turabian Style
Anouar, El H.; Moustapha, Moustapha E.; Taha, Muhammad; Geesi, Mohammed H.; Farag, Zeinab R.; Rahim, Fazal; Almandil, Noor B.; Farooq, Rai K.; Nawaz, Muhammad; Mosaddik, Ashik. 2019. "Synthesis, Molecular Docking and β-Glucuronidase Inhibitory Potential of Indole Base Oxadiazole Derivatives." Molecules 24, no. 5: 963.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.