Chemical Informatics

Synthesis and biological screening of novel thiourea derivatives as potential antihyperglycemics

Background: The prevalence of Type II Diabetes Mellitus is growing in epidemic proportions globally followed by late complications of neuropathy, nephropathy, cardiovascular risks and obesity on increased duration. Although diabetes is among the top national priorities of medical research, diabetes care in India leaves much to be desired. In India, more than half of patients have poor glycaemic control and have vascular complications. Therefore there is a persistant need for exploration of new molecular targets and strategies to develop safer and effective antihyperglycemics which can also cater to the management of long term complications of type-2 diabetes. Intrigued by the benefits of hybrid molecules involving multiple ligands in management of multi-factorial diseases, thiourea derivatives coupled with chalcones moiety have been developed as each of these moieties have independently shown considerable potential antihyperglycemic action.

Aim of work: A new series of hybrid thiourea derivatives were designed and synthesized to meet the structural requirement essential for antihyperglycemic activity. The current work aimed to explore the effect of these hybrid thiourea derivativeson an experimental model of type 2 diabetes.

Methods: Eight different substituted [1-{3-[(2E)-3-phenylprop-2-enoyl] phenyl} thioureas were synthesized using ([N-[(3-acetyl phenyl) carbamothioyl] benzamide] and corresponding benzaldehyde as a starting material. All the compounds were confirmed by means of IR, 1H NMR, and ESIMS and evaluated for in vivoantihyperglycemicactivity by using STZ induced Wister male rat model. Furtherpancreatic β-cell function of each group was assessed by measuring BUN, serum TRIG, HDL cholesterol, LDL cholesterol, serum total proteins.

Result: Administration of low dose Streptozotocin (STZ) to rat, induced hyperglycemia along with considerable augmentation in blood urea nitrogen, creatinine and serum triglycerides markers of renal insufficiency and diabetes induced cardiac complications respectively. Among the six compounds screened, Compound I, V, VI, VII were able to reduce significantly the increased glycemia level to normal within a period of 24 hours in the STZ model along with significant improvement in the blood urea nitrogen and serum triglyceride level by compound I,V.

Conclusion: This observation indicates that compound I-VI have the potential to be an effective antihyperglycemic agent. Studies are underway to assess the renoprotective and cardioprotective effects of these compounds and their possible mode of action.

Author(s):

Tapan Kumar Maity¹ and Satarupa Acharjee^1,2

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