Evaluation of bisindole as potent β-glucuronidase inhibitors: Synthesis and in silico based studies

Khan, Khalid Mohammed; Wadood, Abdul; Taha, Muhammad; Khan, Momin; Naureen, Shagufta; Ambreen, Nida; Hussain, Shafqat; Perveen, Shahnaz; Choudhary, M. Iqbal

doi:10.1016/j.bmcl.2014.02.015

Cited by 48 publications

(17 citation statements)

References 44 publications

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“…Consistent with the excellent inhibitory potencies of indolebased compounds, a library of bis-indoles ( Fig. 36) have been reported as strong bGLU inhibitors [209]. Once more, the importance of (di)hydroxy substitution to potency was prominent.…”

Section: Indole-based Hybridssupporting

confidence: 59%

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

Awolade

Cele

Kerru

et al. 2020

European Journal of Medicinal Chemistry

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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.

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Section: Indole-based Hybridssupporting

confidence: 59%

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

Awolade

Cele

Kerru

et al. 2020

European Journal of Medicinal Chemistry

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“…Earlier, our group reported the leishmanicidal and β-glucurinodase inhibition potential of hydrazides derived from the corresponding esters [35][36][37][38]. In view of the formerly reported work we synthesized hydrazide Schiff bases and screened their potential biological activities [39][40][41][42]. Acylhydrazide Schiff base derivatives 1-28 were synthesized from an acylhyrazide by condensing it with different aromatic aldehydes and acetophenones under reflux conditions in ethanol for 2-3 h (Scheme 1).…”

Section: Chemistrymentioning

confidence: 99%

Phenoxyacetohydrazide Schiff Bases: β-Glucuronidase Inhibitors

et al. 2014

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Phenoxyacetohydrazide Schiff base analogs 1-28 have been synthesized and their in vitro β-glucouoronidase inhibition potential studied. Compounds 1 (IC 50 = 9.20 ± 0.32 µM), 5 (IC 50 = 9.47 ± 0.16 µM), 7 (IC 50 = 14.7 ± 0.19 µM), 8 (IC 50 = 15.4 ± 1.56 µM), 11 (IC 50 = 19.6 ± 0.62 µM), 12 (IC 50 = 30.7 ± 1.49 µM), 15 (IC 50 = 12.0 ± 0.16 µM), 21 (IC 50 = 13.7 ± 0.40 µM) and 22 (IC 50 = 22.0 ± 0.14 µM) showed promising β-glucuronidase inhibition activity, better than the standard (D-saccharic acid-1,4-lactone, IC 50 = 48.4 ± 1.25 µM).

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“…Our previous studies involved benzothiazoles [36] bisindolylmethanes [37] as new and highly potent inhibitors of this enzyme. These findings lead us to understand that other organic classes such as benzimidazoles should also be evaluated against b-glucuronidase enzymes in search of new lead molecules.…”

Section: Introductionmentioning

confidence: 99%