Hypoglycemic, hepatoprotective and molecular docking studies of 5-[(4-chlorophenoxy) methyl]-1, 3, 4-oxadiazole-2-thiol

  • Naureen Shehzadi Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore 54030, Pakistan http://orcid.org/0000-0001-6688-3289
  • Khalid Hussain Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore 54030, Pakistan
  • Nadeem Irfan Bukhari Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore 54030, Pakistan
  • Muhammad Islam Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore 54030, Pakistan
  • Muhammad Tanveer Khan Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan
  • Muhammad Salman Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore 54030, Pakistan
  • Sabahat Zahra Siddiqui Department of Chemistry, Government College University, Lahore 54030, Pakistan
  • Aziz Ur Rehman Department of Chemistry, Government College University, Lahore 54030, Pakistan
  • Muhammad Athar Abbasi Department of Chemistry, Government College University, Lahore 54030, Pakistan
Keywords: Hepatoprotective, Hypoglycemic, Molecular docking

Abstract

The present study aimed at the evaluation of anti-hyperglycemic and hepatoprotective potential of a new drug candidate, 5-[(4-chlorophenoxy) methyl]-1,3,4-oxadiazole-2-thiol (OXCPM) through in vitro and in vivo assays, respectively. The compound displayed excellent dose-dependent ɑ-amylase (28.0-92.0%), ɑ-glucosidase (40.3-93.1%) and hemoglobin glycosylation (9.0%-54.9%) inhibitory effects and promoted the uptake of glucose by the yeast cells (0.2 to 26.3%). The treatment of the isoniazid- and rifampicin- (p.o., 50 mg/kg of each) intoxicated rats with OXCPM (100 mg/kg, p.o.) resulted in restoring the normal serum levels of the non-enzymatic (total bilirubin, total protein and albumin) and bringing about a remarkable decrease in the levels of enzymatic (alanine transaminases, aspartate transaminases and alkaline phosphatase) biomarkers. The molecular docking studies indicated high binding affinity of the compound for hyperglycemia-related protein targets; fructose-1,6-bisphosphatase, beta2-adrenergic receptors and glucokinase. The results indicate that OXCPM may not only reduce hyperglycemia by enzyme inhibition but also the disease complications through protection of hemoglobin glycosylation and hepatic injury.

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Glucose uptake by yeast cells:   4 min 51 sec   Click to watch

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Author Biographies

Naureen Shehzadi, Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore 54030, Pakistan

Senior Lecturer

Khalid Hussain, Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore 54030, Pakistan

Dean 

Nadeem Irfan Bukhari, Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore 54030, Pakistan

Principal

Muhammad Islam, Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore 54030, Pakistan

Assistant Professor

Muhammad Tanveer Khan, Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan

Assistant Professor

Muhammad Salman, Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore 54030, Pakistan

Lecturer

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Published
2018-05-10
How to Cite
Shehzadi, N., K. Hussain, N. Bukhari, M. Islam, M. Khan, M. Salman, S. Siddiqui, A. Rehman, and M. Abbasi. “Hypoglycemic, Hepatoprotective and Molecular Docking Studies of 5-[(4-Chlorophenoxy) Methyl]-1, 3, 4-Oxadiazole-2-Thiol”. Bangladesh Journal of Pharmacology, Vol. 13, no. 2, May 2018, pp. 149-56, doi:10.3329/bjp.v13i2.35514.
Section
Research Articles