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 (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.
Highlights
IntroductionIntroduction β-glucuronidase enzyme that catalyzes the extracellular matrix cancer and normal cells β-glucuronidase is is anan enzyme that catalyzes the extracellular matrix ofof cancer and normal cells and catalyzes glycosaminoglycans of the cell membrane
Introduction β-glucuronidase enzyme that catalyzes the extracellular matrix cancer and normal cells β-glucuronidase is is anan enzyme that catalyzes the extracellular matrix ofof cancer and normal cells and catalyzes glycosaminoglycans of the cell membrane.This catalysis is important for cancer and catalyzes glycosaminoglycans of the cell membrane
Β-glucuronidase has been are caused by the increase level of β-glucuronidase activity [3,4,5,6]. β-glucuronidase has been usedused as an important tool the detection realmonitoring, time monitoring, therapies, diagnosis early anasimportant tool in thein detection of realof time clinicalclinical therapies, diagnosis in early in stage, stage, used inmarker tumor[7,8]
Summary
Introduction β-glucuronidase enzyme that catalyzes the extracellular matrix cancer and normal cells β-glucuronidase is is anan enzyme that catalyzes the extracellular matrix ofof cancer and normal cells and catalyzes glycosaminoglycans of the cell membrane. Colon carcinoma and neoplasm bladder are caused by the increase level of β-glucuronidase activity [3,4,5,6]. Compounds that containedoxadiazole oxadiazolering ring their structures display biological properties including anticancer [20],[20], cytotoxic andand antimicrobial [21], anticonvulsant [22], many biological properties including anticancer cytotoxic antimicrobial [21], anticonvulsant antiepileptic [23], anti-TB [24], and anti-allergic activities [25]. Our research group has reported various heterocyclic compounds classes asas potent inhibitors ofof β-glucuronidase [28,29,30,31,32,33,34,35].
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