Therapeutic significance of β-glucuronidase activity and its inhibitors: A review

Abstract

BiomarkerEnzyme inhibition Molecular target Structure activity relationship a b s t r a c tThe emergence of disease and dearth of effective pharmacological agents on most therapeutic fronts, constitutes a major threat to global public health and man's existence. Consequently, this has created an exigency in the search for new drugs with improved clinical utility or means of potentiating available ones. To this end, accumulating empirical evidence supports molecular target therapy as a plausible egress and, b-glucuronidase (bGLU) e a lysosomal acid hydrolase responsible for the catalytic deconjugation of b-D-glucuronides has emerged as a viable molecular target for several therapeutic applications. The enzyme's activity level in body fluids is also deemed a potential biomarker for the diagnosis of some pathological conditions. Moreover, due to its role in colon carcinogenesis and certain drug-induced dose-limiting toxicities, the development of potent inhibitors of bGLU in human intestinal microbiota has aroused increased attention over the years. Nevertheless, although our literature survey revealed both natural products and synthetic scaffolds as potential inhibitors of the enzyme, only few of these have found clinical utility, albeit with moderate to poor pharmacokinetic profile. Hence, in this review we present a compendium of exploits in the present millennium directed towards the inhibition of bGLU. The aim is to proffer a platform on which new scaffolds can be modelled for improved bGLU inhibitory potency and the development of new therapeutic agents in consequential.

Nutritional Value and Biological Activity of Gluten-Free Bread Enriched with Cricket Powder

“…The level of β-glucuronidase (β-Glu) activity in body fluids is considered a potential biomarker in the diagnosis of certain intestinal pathological conditions [ 57 ]. Therefore, the search for potent β-Glu inhibitors in the human intestinal microflora has attracted increasing attention over the years [ 58 ], due to its role in colon carcinogenesis In particular, work is underway to discover natural dietary inhibitors of this enzyme. To date, the main strategy for reducing or eliminating the gastrointestinal toxicity caused by bacterial β-Glu is by administration of antibiotics [ 59 , 60 ], but plant food and herbal medicines are a promising source of bacterial inhibitors as well [ 58 , 61 , 62 ].…”

Connecting the dots: targeting gut microbiota in drug toxicity

“…Some natural products such as quercetin can not only generate protective metabolites by gut microbiota but also function as βglucuronidase inhibitors. However, the clinical utilization of currently discovered βglucuronidase inhibitors is limited by poor pharmacokinetic profile (Awolade et al, 2020). Still and all, βglucuronidase may serve as a potent target in respiting drug toxicity.…”

Rational Design, Synthesis, In Vitro, and In Silico Studies of Dihydropyrimidinone Derivatives as β-Glucuronidase Inhibitors

“…Dihydropyrimidinones have been identified to possess a wide range of applications in pharmacology and medicinal chemistry including anticancer [21], antiinflammatory [22], antimicrobial [23], antidiabetic, and antioxidant agents [24]. is skeleton also showed a broad spectrum of biological activities including calcium channel antagonism/inhibition, Eg5 kinesin, and topoisomerase I inhibitor [25]. Considering β-glucuronidase inhibition, dihydropyrimidone and pyrimidine structures were first reported as a successful example in rational drug design against β-glucuronidase [26,27].…”