SYNTHESIS AND EVALUATION OF SOME NEW 2-(5-(4-BENZAMIDOBENZYLIDENE)-2,4DIOXOTHIAZOLIDIN-3-YL)ACETIC ACID ANALOGS AS ALDOSE REDUCTASE INHIBITORS

Jyoti Pandey; Arshad Ali; Arun Kumar Gupta

doi:10.22159/ajpcr.2017.v10i1.12073

Authors

Jyoti Pandey
Arshad Ali
Arun Kumar Gupta

DOI:

https://doi.org/10.22159/ajpcr.2017.v10i1.12073

Abstract

Objective: Aldose reductase (ALR) enzyme plays a significant role in conversion of excess amount of glucose into sorbitol in diabetic condition, inhibitors of which decrease the secondary complication of diabetes mellitus. Scarce treatment of diabetic complications has motivated our interest for the search of new aldose reductase inhibitors (ARIs) endowed with more favorable biological properties.

Methods: Newer (4-(benzamidobenzylidene)-2,4-dioxothiazolidin-3-yl) acetic acid derivatives were synthesized, and these compound were evaluated for their ARI and antidiabetic activity.

Results: ARI activity of synthesized compounds was found in the range of 57.8-71.9% at 5Âµg/mL. Similarly, synthesized compounds decrease blood glucose level in the range of 64.4-70.5 mg/dl at 15 mg/kg body weight.

Conclusion: (E)-2-(5-(4-(substituted benzamido)benzylidene)-2,4-dioxothiazolidin-3-yl)acetic acid analogs shows comparable ARI as well as antidiabetic activity. These new class of compounds might be address the diabetic complications with safety.

Keywords: Aldose reductase inhibitors, Diabetes mellitus, N-acetic acid-2,4-thiazolidinediones.

Downloads

Download data is not yet available.

References

Bastaki S. Diabetes mellitus and its treatment. Int J Diabetes Metab 2005;13:111-34.

Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with Type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352(9131):837-53.

Anil Kumar P, Bhanuprakash Reddy G. Focus on molecules: Aldose reductase. Exp Eye Res 2007;85(6):739-40.

Mansour MA. Aldose reductase in the retina. Curr Enzym Inhib 2007;3:49-60.

Agrawal YP, Agrawal MY, Gupta AK. Emerging molecular targets for the treatment and management of diabetes mellitus - A review. Int J Pharm Sci 2013;5:2000-15.

Yabe-Nishimura C. Aldose reductase in glucose toxicity: A potential target for the prevention of diabetic complications. Pharmacol Rev

;50(1):21-33.

Srivastava SK, Ramana KV, Bhatnagar A. Role of aldose reductase and oxidative damage in diabetes and the consequent potential for therapeutic options. Endocr Rev 2005;26(3):380-92.

Brownlee M. The pathobiology of diabetic complications: A unifying mechanism. Diabetes 2005;54(6):1615-25.

Agrawal YP, Agrawal MY, Gupta AK. Design, synthesis and evaluation of rhodanine derivatives as aldose reductase inhibitors. Chem Biol Drug Des 2015;85(2):172-80.

Costantino L, Rastelli G, Vianello P, Cignarella G, Barlocco D. Diabetes complications and their potential prevention: Aldose reductase inhibition and other approaches. Med Res Rev 1999;19(1):3-23.

Costantino L, Rastelli G, Gamberini MC, Barlocco D. Pharmacological approaches to the treatment of diabetic complications. Expert Opin Ther Patents 2000;10(8):1245.

Castaner J, Prous J. Monograph: Epalrestat. Drugs Future 1987;12:336.

Bruno G, Costantino L, Curinga C, Maccari R, Monforte F, NicolÃ³ F, et al. Synthesis and aldose reductase inhibitory activity of 5-arylidene-

,4-thiazolidinediones. Bioorg Med Chem 2002;10(4):1077-84.

Maccari R, OttanÃ R, Curinga C, Vigorita MG, Rakowitz D, Steindl T, et al. Structure-activity relationships and molecular modelling of

-arylidene-2,4-thiazolidinediones active as aldose reductase inhibitors. Bioorg Med Chem 2005;13(8):2809-23.

Maccari R, OttanÃ R, Ciurleo R, Vigorita MG, Rakowitz D, Steindl T, et al. Evaluation of in vitro aldose redutase inhibitory activity

of 5-arylidene-2,4-thiazolidinediones. Bioorg Med Chem Lett 2007;17(14):3886-93.

Lee YS, Hodoscek M, Kador PF, Sugiyama K. Hydrogen bonding interactions between aldose reductase complexed with NADP(H) and inhibitor tolrestat studied by molecular dynamics simulations and binding assay. Chem Biol Interact 2003;143-144:307-16.

El-Kabbani O, Ruiz F, Darmanin C, Chung RP. Aldose reductase structures: Implications for mechanism and inhibition. Cell Mol Life Sci 2004;61(7-8):750-62.

Da Settimo F, Primofiore G, La Motta C, Salerno S, Novellino E, Greco G, et al. Spirohydantoin derivatives of thiopyrano[2,3-b]pyridin-

(4H)-one as potent in vitro and in vivo aldose reductase inhibitors. Bioorg Med Chem 2005;13(2):491-9.