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Synthesis, Biological Screening and in Silico Studies of Chalcone Based Novel Phenyl Urea Derivatives as Potential Antihyperglycemics


Affiliations
1 Department of Pharmaceutical Technology, Synthetic and Natural Product Research Laboratory, Jadavpur University, Jadavpur, Kolkata-700032, West Bengal, India
2 Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India
 

Aim: Current work was aimed to explore the effect of synthesized novel chalcone based1-(4"-methoxyphenyl)-3-{4- [(2E)-3-phenylprop-2-enoyl] phenyl} ureaderivatives, on adult male Wister rats in an experimental model of type 2 diabetes.

Methods: Type 2 Diabetes was induced in overnight fasted rats by a high fat diet followed by a single intraperitoneal injection of low dose streptozotocin (35mg/kg body weight) leading to hyperglycemia and considerable augmentation in blood urea nitrogen and creatinine levels. Treatment with compounds 2(a-d) and 3(a-c)(dose; 30mg/kg) continued for 28 days followed by oral glucose tolerance test. Docking studies of synthesized compounds with ligand binding domain of the human peroxisome proliferator activated receptor gamma-2(2PRG) were performedto correlate the antihypergycemic activity for possible mode of action.

Result: Oral administration of compounds 2(a-d) and 3(a-c)in 35mg/kg for 4 weeks reduced blood glucose level significantly by 68-71% and 71-75% respectively comparable to that of glipizide(80%) in a dose of 1mg/kg/day coupled with significant reduction (p≤0.05) in the increased blood urea nitrogen and serum triglyceride level. Compound 2c have been found most active on the PPAR gamma receptor displaying docking score (-21) comparable to reference ligands Rosiglitazone and pioglitazone.

Conclusion: This observation indicates that chalcone based novel phenylureas have the potential to be an effective antihypergycemic agent with probable PPAR gamma agonistic action.


Keywords

Chalcone, Urea, Glucose Tolerance Test, PPAR Gamma.
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  • http://timesofindia.indiatimes.com/life-style/health-fitness/healthnews/ India-is-thediabetes- capital-of-the-world/articleshow/50753461.cms,Malik R, 2016, [Cited 2016,Jan 28]

  • Gisela W, Insulin and insulin resistance, Clin. Biochem. Rev.2010; 26:119-139.

  • MahapatraDK, AsatiV, BhartiSK. Chalcones and their therapeutic targets for the management of diabetes: structural and pharmacological perspectives. Eur. J Med. Chem.2015; 92: 839-865.

  • JawaleDV, PratapUR, RahujaN,SrivastavaAK, ManeRA.Synthesis and antihyperglycemic evaluation of new2,4-thiazolidinediones having biodynamic arylsulfonylureamoieties,Bioorg. & Med. Chem. Lett.2012; 22:436-439.

  • ShuklaP, SinghAB, SrivastavaAK , PratapR. Chalcone based aryloxypranolamines as potential antihyperglycemic agent, Bioorg.med chem.2007;17: 799-802.

  • SeoWD, JinHK, KangJE, RyuHW, LongMJC, LeeHS Yang MS, ParkKH, Sulfonamide chalcone as a new class of alpha-glucosidase inhibitors, Bioorg. Med. Chem. Lett.2005;15: 5514-5516.

  • KharbandaC, AlamMS, HamidH, JavedK, DhulapA, BanoS, AliY, Antidiabetic effect of novel benzenesulfonylureas as PPAR-γ agonists and their anticancer effect, Bioorg.Med.Chem.Lett.2015;25: 4601-4605.

  • KharbandaC, AlamMS, HamidH, JavedK, DhulapA, BanoS, Ali Y, Novel benzenesulfonylureas containing thiophenylpyrazoline moiety as potential antidiabetic andanticancer agents, Bioorg.Med.chem.Lett.2015;24: 52985303.

  • FrankRL,SmithPV.Org. Synth.1948;28: 89, DOI: 10.15227/orgsyn.028.0089, [Accessed on 20 May, 2014].

  • Vasudeva RA, Yejella RP, Annapurna A, Guntuku GS, Doddi BR, Vutla VR, Anagani SR et.al, Synthesis, characterization and biological evaluation of some novel 2,4- thiazolidinediones as potential cytotoxic, antimicrobial and antihyperglycemic agents, Bioorg. Med. Chem. Lett.2012; 22:6442–6450.

  • Bandgar BP, Gawande SS, Bodade RG,Totre JV, Khobragade CN, Synthesis and biological evaluation of simple methoxylated chalcones as anticancer, antiinflammatory and antioxidant agents,Bioorg. Med. Chem.2010; 18:1364–1370.

  • SkovsoS. Modeling type 2 diabetes in rats using high fat diet and streptozotocin.J Diabetes Investig.2014; 5: 349-358,DOI:10.1111/jdi.12235.

  • L Crane, Anastassiadou M, Salomé Ehage, StiglianiJL, Baziard-Mouysset G, Payard, JM..Leger M, Bizot-Espiard JG, Ktorza A., Imidazoline derivatives with potent antihyperglycemic activity in a rat model of type 2 diabetes, Bioorg Med chem.2006;14:7419-33.

  • Roy S, Majumdar S, Singh AK, Ghosh B, Ghosh N, Manna S, Chakraborty S, Mallick S, Synthesis, Characterization, Antioxidant Status, and Toxicity Study of Vanadium–Rutin Complex in Balb/c Mice, Biol. Trace. Elem. Res.2015; 166 (2):183-200.

  • Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao P. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening.Pharmacol Res, 2005; 52: 313–320.

  • Saha HR, Sarkar BC, Khan SA, Sana NK, Choudhury S, A comparative study of thyroid hormone and lipid status in diabetic and non diabetic adults.Open. Access. Sci.Reports.2012; 1(9):1–5.

  • HenryNG, Yuan-LiZ, AntonioH, Regulation of plasma triglycerides ininsulin resistance and diabetes. Arch Med Res.2005; 36: 232–240.

  • Oliveira HC, Dos S, Grigulo MP, Lima LL, Martins DTO, Lima JCS, Stoppiglia LF, Lopes, Kawashita CF, Hypoglycemic and antihyperglycemic effect of begonia malabarica in STZrats, N.F. J Ethnopharmacol.2008;115: 515 –519.

  • Jangra M, Sharma S, Kumar M, Evaluation of antihyperglycemic activity of dodonaea viscosa leaves in normal and stzdiabetic rats.Int. J Pharm. Pharm. Sci.2011;3: 69-74.

  • TsakovskaI, Al SharifM, Alov P, Diukendjieva A, Fioravanzo E, CroninMTD, Pajeva I, Molecular Modelling Study of the PPARγ Receptor in Relationto the Mode of Action/Adverse Outcome Pathway Framework for Liver Steatosis,Int. J. Mol. Sci.2014;15: 7651-7666.

  • GuaschL, Sala E, Castell-Auví A, CedoL, Liedl KR, Wolber G, Muehlbacher M, MuleroM,PinentM,ArdévolA, Identification of PPARgamma partial agonists of natural origin (I): Development of a virtual screening procedure and in vitro validation. PLoS One.2012; 7: e50816.

  • Jung SH, Park SY, Kim-pak Y, Lee HK, Park KS, Shin KH OhuchiK, Keum SR, Lim SS, Synthesis and PPAR-γLigand-Binding Activity of the New Series of 2Hydroxychalcone and Thiazolidinedione Derivatives,Chem. Pharm. Bull.2006;54: 368—371.

  • HI Kim,YH Ahn, Role of Peroxisome Proliferator–Activated Receptor in the glucosesensing apparatus of liver and cells, Diabetes.2004; 1:S60-65.


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  • Synthesis, Biological Screening and in Silico Studies of Chalcone Based Novel Phenyl Urea Derivatives as Potential Antihyperglycemics

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Authors

Satarupa Acharjee Sengupta
Department of Pharmaceutical Technology, Synthetic and Natural Product Research Laboratory, Jadavpur University, Jadavpur, Kolkata-700032, West Bengal, India
Tapan K. Maity
Department of Pharmaceutical Technology, Synthetic and Natural Product Research Laboratory, Jadavpur University, Jadavpur, Kolkata-700032, West Bengal, India
Subir Samanta
Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India

Abstract


Aim: Current work was aimed to explore the effect of synthesized novel chalcone based1-(4"-methoxyphenyl)-3-{4- [(2E)-3-phenylprop-2-enoyl] phenyl} ureaderivatives, on adult male Wister rats in an experimental model of type 2 diabetes.

Methods: Type 2 Diabetes was induced in overnight fasted rats by a high fat diet followed by a single intraperitoneal injection of low dose streptozotocin (35mg/kg body weight) leading to hyperglycemia and considerable augmentation in blood urea nitrogen and creatinine levels. Treatment with compounds 2(a-d) and 3(a-c)(dose; 30mg/kg) continued for 28 days followed by oral glucose tolerance test. Docking studies of synthesized compounds with ligand binding domain of the human peroxisome proliferator activated receptor gamma-2(2PRG) were performedto correlate the antihypergycemic activity for possible mode of action.

Result: Oral administration of compounds 2(a-d) and 3(a-c)in 35mg/kg for 4 weeks reduced blood glucose level significantly by 68-71% and 71-75% respectively comparable to that of glipizide(80%) in a dose of 1mg/kg/day coupled with significant reduction (p≤0.05) in the increased blood urea nitrogen and serum triglyceride level. Compound 2c have been found most active on the PPAR gamma receptor displaying docking score (-21) comparable to reference ligands Rosiglitazone and pioglitazone.

Conclusion: This observation indicates that chalcone based novel phenylureas have the potential to be an effective antihypergycemic agent with probable PPAR gamma agonistic action.


Keywords


Chalcone, Urea, Glucose Tolerance Test, PPAR Gamma.

References