Synthesis of novel inhibitors of β-glucuronidase based on benzothiazole skeleton and study of their binding affinity by molecular docking

Khalid Mohammed Khan, Fazal Rahim, Sobia Ahsan Halim, Muhammad Taha, Momin Khan, Shahnaz Perveen, Zaheer-Ul-Haq, Osman Mesaik Mohammed Ahmed Hassan, M. Iqbal Choudhary

Research output: Contribution to journalArticle

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Abstract

Benzothiazole derivatives 1-26 have been synthesized and their in vitro β-glucuronidase potential has been evaluated. Compounds 4 (IC 50 = 8.9 ± 0.25 μM), 5 (IC 50 = 36.1 ± 1.80 μM), 8 (IC 50 = 8.9 ± 0.38 μM), 13 (IC 50 = 19.4 ± 1.00 μM), 16 (IC 50 = 4.23 ± 0.054 μM), and 18 (IC 50 = 2.26 ± 0.06 μM) showed β-glucuronidase activity potent than the standard (d-saccharic acid 1,4-lactone, IC 50 = 48.4 ± 1.25 μM). Compound 9 (IC 50 = 94.0 ± 4.16 μM) is found to be the least active among the series. All active analogs were also evaluated for cytotoxicity and none of the compounds showed any cytotoxic effect. Furthermore, molecular docking studies were performed using the gold 3.0 program to investigate the binding mode of benzothiazole derivatives. This study identifies a novel class of β-glucuronidase inhibitors.

Original languageEnglish
Pages (from-to)4286-4294
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number14
DOIs
Publication statusPublished - 15 Jul 2011
Externally publishedYes

Fingerprint

Glucuronidase
Skeleton
Derivatives
Cytotoxicity
Gold
benzothiazole

Keywords

  • β-Glucuronidase inhibition
  • Benzothiazole
  • Cytotoxicity
  • Glucuronosyl-O-bonds
  • gold
  • Molecular docking
  • Structure-activity relationship (SAR)

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Synthesis of novel inhibitors of β-glucuronidase based on benzothiazole skeleton and study of their binding affinity by molecular docking. / Khan, Khalid Mohammed; Rahim, Fazal; Halim, Sobia Ahsan; Taha, Muhammad; Khan, Momin; Perveen, Shahnaz; Zaheer-Ul-Haq; Mohammed Ahmed Hassan, Osman Mesaik; Iqbal Choudhary, M.

In: Bioorganic and Medicinal Chemistry, Vol. 19, No. 14, 15.07.2011, p. 4286-4294.

Research output: Contribution to journalArticle

Khan, KM, Rahim, F, Halim, SA, Taha, M, Khan, M, Perveen, S, Zaheer-Ul-Haq, Mohammed Ahmed Hassan, OM & Iqbal Choudhary, M 2011, 'Synthesis of novel inhibitors of β-glucuronidase based on benzothiazole skeleton and study of their binding affinity by molecular docking', Bioorganic and Medicinal Chemistry, vol. 19, no. 14, pp. 4286-4294. https://doi.org/10.1016/j.bmc.2011.05.052
Khan, Khalid Mohammed ; Rahim, Fazal ; Halim, Sobia Ahsan ; Taha, Muhammad ; Khan, Momin ; Perveen, Shahnaz ; Zaheer-Ul-Haq ; Mohammed Ahmed Hassan, Osman Mesaik ; Iqbal Choudhary, M. / Synthesis of novel inhibitors of β-glucuronidase based on benzothiazole skeleton and study of their binding affinity by molecular docking. In: Bioorganic and Medicinal Chemistry. 2011 ; Vol. 19, No. 14. pp. 4286-4294.
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