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Molecules 2019, 24(5), 963; https://doi.org/10.3390/molecules24050963

Synthesis, Molecular Docking and β-Glucuronidase Inhibitory Potential of Indole Base Oxadiazole Derivatives

1
Department of Chemistry, College of Science and Humanities, Prince Sattam bin Abdulaziz University, P.O. Box 83, Al Kharj 11942, Saudi Arabia
2
University Central Laboratory, College of Science and Humanities, Prince Sattam bin Abdulaziz University, P.O. Box 83, Al Kharj 11942, Saudi Arabia
3
Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
4
Chemistry Department, Faculty of Science, Fayoum University, Fayoum 63514, Egypt
5
Department of Chemistry, Hazara University, Mansehra, Khyber Pakhtunkhwa 21300, Pakistan
6
Department of Neuroscience Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
7
Department of Nano-Medicine Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
*
Authors to whom correspondence should be addressed.
Received: 14 February 2019 / Revised: 1 March 2019 / Accepted: 3 March 2019 / Published: 8 March 2019
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Abstract

β-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 (122) 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
Keywords: synthesis; indole; oxadiazole; β-glucuronidase; molecular docking; SAR synthesis; indole; oxadiazole; β-glucuronidase; molecular docking; SAR
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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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.

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