Synthesis of benzimidazole derivatives as potent β-glucuronidase inhibitors

Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Selvaraj, Manikandan; Rashwan, Hesham Mohamed Ezzeldin; Farhanah, Fatin Ummi; Rahim, Fazal; Selvarajan, Kesavanarayanan Krishnan; Ali, Muhammad

doi:10.1016/j.bioorg.2015.05.010

Cited by 52 publications

(16 citation statements)

References 48 publications

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“…22) was found with strongest inhibitory potency (IC 50 ¼ 6.33 mM). Interestingly, introducing 5,7-dichloro unit on benzimidazole nucleus gave remarkable results as previously inactive molecules gained significant activity [193]. Compound 111 emerged as the most potent inhibitor overall with IC 50 ¼ 4.48 mM and 11-fold stronger than D-SAL.…”

Section: 214mentioning

confidence: 99%

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: 214mentioning

confidence: 99%

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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“…Taha et al subjected 25 benzimidazole derivatives with reported activity against β‐glucuronidase inhibitors (Scheme ). Compound 448 was found to be most potent with IC 50 = 48.4 ± 1.25 μM as compared to standard drug d ‐saccharic acid 1,4‐lactone with IC 50 = 48.4 ± 1.25 μM (Table ).…”

Section: Pharmacological and Synthetic Profiles Of Benzimidazole Derimentioning

confidence: 99%

Benzimidazole Scaffold as Anticancer Agent: Synthetic Approaches and Structure–Activity Relationship

Shrivastava

Naim

Alam

et al. 2017

Archiv der Pharmazie

118

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Cancer, also known as malignant neoplasm, is a dreadful disease which involves abnormal cell growth having the potential to invade or spread to other parts of the body. Benzimidazole is an organic compound that is heterocyclic and aromatic in nature. It is a bicyclic compound formed by the fusion of the benzene and imidazole ring systems. It is an important pharmacophore and a privileged structure in medicinal chemistry. According to the World Health Organisation (2015 survey), one in six deaths is due to cancer around the globe, accounting for 8.8 million deaths of which 70% of the cases were from low- and middle-income countries. In the efforts to develop suitable anticancer drugs, medicinal chemists have focussed on benzimidazole derivatives. This review article covers the current development of benzimidazole-based anticancer agents along with the synthetic approaches and structure-activity relationships (SAR).

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“…In the continuation of our research on enzyme inhibition (Rahim et al, 2015a,b;Taha et al, 2015d;Abdullah et al, 2015;Khan et al, 2014e) 3,4,5-trihydroxybenzohydrazones Synthesis of 3,4,5-trihydroxybenzohydrazone and evaluation of inhibition potential…”

Section: Chemistrymentioning

confidence: 98%

Synthesis of 3,4,5-trihydroxybenzohydrazone and evaluation of their urease inhibition potential

Taha

Khan

Arshad

et al. 2019

Arabian Journal of Chemistry

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In the continuation of our work to synthesize enzyme inhibitors, we synthesized 3,4,5-tri hydroxybenzohydrazones (1-19) from 3,4,5-trihydroxybenzohydrazide, which were obtained from methyl 3,4,5-trihydroxybenzoate by refluxing with hydrazine hydrate. All the synthesized compounds were characterized by different spectroscopic methods. The synthesized compounds were evaluated for urease inhibition and showed excellent results, close to the standards thiourea. The kinetic studies on the five most active compounds 6, 10, 14, 16 and 18 were carried out to determine their mode of inhibition and dissociation constant K i . The compounds 6 and 16 were found to be competitive inhibitors with K i values 19.1 and 10.53 lM, respectively, while the compounds 10, 14 and 18 were found to be mixed-type of inhibitors with K i values in the range of 18.4-21.7 lM. ª 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Synthesis of benzimidazole derivatives as potent β-glucuronidase inhibitors

Cited by 52 publications

References 48 publications

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

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

Benzimidazole Scaffold as Anticancer Agent: Synthetic Approaches and Structure–Activity Relationship

Synthesis of 3,4,5-trihydroxybenzohydrazone and evaluation of their urease inhibition potential

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