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Novel Hybrids of Pyrazolidinedione and Benzothiazole as TZD Analogues. Rationale, Design, Synthesis and In Vivo Anti-Diabetic Evaluation

[ Vol. 15 , Issue. 6 ]


Michelyne Haroun*   Pages 622 - 631 ( 10 )


Background: The development of new classes of blood glucose–lowering medications has elevated the number of treatment opportunities available for type 2 diabetes. Nevertheless, long term complicated treatments and side effects of available antidiabetic therapies have urged huge demands for effective affordable anti diabetic agents that can lessen negative heath consequences. In this sense, the exploration of alternative medicinal remedies associated with new significant antidiabetic efficiencies with minimized adverse effects is an active domain of research.

Objective: The aim of this study was to synthesize a series of benzothiazole-pyrazolidinedione hybrids and evaluate their antidiabetic activity along with molecular docking and in silico analysis.

Methods: The hybrids were synthesized by a multi-step synthesis and were further subjected for in vivo anti-hyperglycemic assessment on rat models of type II diabetes. Molecular modelling study was undertaken against peroxisome proliferator-activated receptor γ (PPARγ) to highlight possible key interactions.

Results: Docking studies revealed that appropriate substituents on benzothiazole ring interact favorably with the hydrophobic Ω-pocket of PPARγ binding site resulting in improving their anti-hyperglycemic activity. All synthesized hybrids manifested promising anti-hyperglycemic potency. Excitingly, 5a, 5b and 5c were even more potent than the standard drug.

Conclusion: The newly synthesized hybrids can be considered as a new class of antidiabetic agents and this study provided useful information on further optimization.


Benzothiazole, Pyrazolidinedione, PPARgamma, Ligand binding domain: Ω-loop, Molecular modeling, Antihyperglycemic activity.


Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982

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