Skip to main content
SpringerLink
Log in

Synthesis of New Thiazolidine-2,-4-dione-azole Derivatives and Evaluation of Their α-Amylase and α-Glucosidase Inhibitory Activity

  • Research Paper
  • Published:
Iranian Journal of Science and Technology, Transactions A: Science Aims and scope Submit manuscript

Abstract

In a search for α-amylase and α-glucosidase inhibitors to treat type 2 diabetes in this study, a new series of thiazolidine-2,4-dione derivatives with azole heterocyclic compounds were designed and synthesized via Knoevenagel condensation for the first time. These synthesized compounds are characterized by IR, 1H NMR, 13C NMR, DEPT-135, and HRMS. All the synthesized compounds were evaluated for α-amylase and α-glucosidase inhibitory activity using acarbose as standard. The lipophilicity (C log P) and molar refractivity (MR) for the compounds were also studied. Structure–activity relationship study (SAR) revealed that compounds 14a–c exhibited maximum inhibition due to the presence of fluorine in a hydrophobic site of aromatic phenyl amine at the seventh position of azaindole. To further verify the effect of C log P of substituents and MR on biological activity, calculation of C log P and MR (molecular refractivity) parameter of all compounds have done using ChemDraw software. Compounds 14a–c found to show higher inhibition due to higher value of C log P (14a = 6.49, 14b = 5.63, 14c = 6.45) and MR (14a = 125, 14b = 117, 14c = 123). These properties make compounds 14a–c to have more inhibitory activity. Among the tested compounds, 14a–c showed inhibition in the range of standard acarbose at the concentration of 250 µg/ml against α-amylase and α-glucosidase.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Scheme 1
Scheme 2
Scheme 3
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Alegaon SG, Alagawadi KR, Sonkusare PV, Chaudhary SM, Dadwe DH, Shah AS (2012) Novel imidazo[2,1-b][1,3,4]thiadiazole carrying rhodanine-3-acetic acid as potential antitubercular agents. Bioorg Med Chem Lett 22:1917–1921

    Article  Google Scholar 

  • American Diabetes Association (2009) Diabetes Care 32(Suppl 1):S62–S67

    Article  Google Scholar 

  • Ansari KF, Lal C (2009) Synthesis, physicochemical properties and antimicrobial activity of some new benzimidazole derivatives. Eur J Med Chem 44:4028–4033

    Article  Google Scholar 

  • Asati V, Mahapatra DK, Bharti SK (2014) Thiazolidine-2,4-diones as multi-targeted scaffold in medicinal chemistry. Potential anticancer agents. Eur J Med Chem 87:814–833

    Article  Google Scholar 

  • AshokKumar J, Tiwari AK, Saidachary G, Kishor C, Anand Kumar D, Ali Z, Sridhar B, Addlagatta A, China Raju B (2014) Pancreatic a-amylase inhibition and free radical scavenging activity of substituted pyranochromenone derivatives. Med Chem Res 23:2821–2833

    Article  Google Scholar 

  • Azizmohammadi M, Khoobi M, Ramazani A, Emami S, Zarrin A, Firuzi O, Miri R, Shafiee A (2013) 2H-chromene derivatives bearing thiazolidine-2,4-dione, rhodanine or hydantoin moieties as potential anticancer agents. Eur J Med Chem 5:15–22

    Article  Google Scholar 

  • El-Sharief MAMS, Moussa Z, El-Sharief AMS (2011) Synthesis, characterization, and derivatization of some novel types of fluorinated mono and bis-imidazolidineiminothiones with antitumor, antiviral, antibacterial and antifungal activities. J Fluorine Chem 132:596–611

    Article  Google Scholar 

  • Guan A, Liu C, Huang G, Li H, Hao S, Xu Y, Xie Y, Li Z (2014) Synthesis and fungicidal activity of fluorine-containing chlorothalonil derivatives. J Fluor Chem 160:82–87

    Article  Google Scholar 

  • Guo S, Wang Y, Sun C, Li J, Zou D, Wu Y, Wu Y (2013) Efficient synthesis of 2-arylamino substituted pyridinyl nitriles by Buchwald-Hartwig amination. Tetrahedron Lett. 54:3233–3237

    Article  Google Scholar 

  • Jawale DV, Pratap UR, Rahuja N, Srivastava AK, Mane RA (2012a) Synthesis and anti hyperglycemic evaluation of new 2,4-thiazolidinediones having biodynamic aryl sulfonylurea moieties. Bioorg Med Chem Lett 22:436–439

    Article  Google Scholar 

  • Jawale DV, Pratap UR, Mane RA (2012b) An alternative synthetic route for anantidiabetic drug, rosiglitazone. Bioorg Med Chem Lett 22:924–928

    Article  Google Scholar 

  • Khazi MIA, Belavagi NS, Kim KR, Gong YD, Khazi IAM (2013) Synthesis, hypoglycaemic, hypolipidemic and PPARγ agonist activities of 5-(2-alkyl/aryl-6-Arylimidazo[2,1-b][1,3,4]thiadiazol-5-yl)methylene-1,3-thiazolidinediones. Chem Biol Drug Des 82:147–155

    Article  Google Scholar 

  • Kumar BRP, Soni M, Santhosh Kumar S, Singh K, Nasir Baig RB, Adhikary L (2011) Synthesis, glucose uptake activity and structureeactivity relationships of some novel glitazones incorporated with glycine, aromatic and alicyclic amine moieties via two carbon acyl linker. Eur J Med Chem 46:835–844

    Article  Google Scholar 

  • Lee HW, Yang JY, Lee HS (2014) Quinoline-2-carboxylic acid isolated from ephedrapachyclada and its structural derivatives show inhibitory effects against α-Glucosidase and α-amylase. J Korean Soc Appl Biol Chem 57:441–444

    Article  Google Scholar 

  • Liu XF, Zheng CJ, Sun LP, Liu XK, Piao HR (2011) Synthesis of new chalcone derivatives bearing 2,4-thiazolidinedione and benzoic acid moieties as potential anti-bacterial agents. Eur J Med Chem 46:3469–3473

    Article  Google Scholar 

  • Lukmantara AY, Kalinowski DS, Kumar N, Richardson DR (2013) Structure–activity studies of 4-phenylsubstituted 2’-benzoylpyridine thiosemicarbazones with potent and selective anti-tumour activity. Org Biomol Chem 11(37):6414–6425

    Article  Google Scholar 

  • Maccari R, Ciurleo R, Paoli P, Manao G, Vigorita MG, Ottana R, Steindl T, Jacomelli M, Camici G (2007) 5-Arylidene-2,4-thiazolidinediones as inhibitors of protein tyrosine phosphatases. Bioorg Med Chem 15:5137–5149

    Article  Google Scholar 

  • Maccari R, Ottanà R, Ciurleo R, Rakowitz D, Matuszczak B, Laggner C, Langer T (2008) Synthesis, induced-fit docking investigations, and in vitro aldose reductase inhibitory activity of non-carboxylic acid containing 2,4-thiazolidinedione derivatives. Bioorg Med Chem 16:5840–5850

    Article  Google Scholar 

  • Magdole P, Meciarova M, Toma S (2001) Ultrasound effect on the synthesis of 4-alkyl-(aryl) amino benzaldehyde. Tetrahedron 57:4781–4785

    Article  Google Scholar 

  • Matysiak J (2007) Evaluation of electronic, lipophilic and membrane affinity effects on antiproliferative activity of 5-substituted-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles against various human cancer cells. Eur J Med Chem 42(7):940–947

    Article  Google Scholar 

  • Nazreen S, Alam MS, Hamid H, Yar MS, Dhulap A, Alam P, Pasha MAQ, Bano S, Alam MM, Haider S, Kharbanda C, Ali Y, Pillai KK (2014) Thiazolidine-2,4-diones derivatives as PPAR-γ agonists: synthesis, molecular docking, in vitro and in vivo antidiabetic activity with hepatotoxicity risk evaluation and effect on PPAR-γ gene expression. Bioorg Med Chem Lett 24:3034–3042

    Article  Google Scholar 

  • Neogi P, Cheng J, Lakner FJ, Dey D, Medicherla S, Gowri M, Nag B, Sharma SD, Pickford LB, Gross C (2003) Synthesis and structure—activity relationship studies of cinnamic acid-based novel thiazolidinedione antihyperglycemic agents. Bioorg Med Chem 11:4059–4067

    Article  Google Scholar 

  • Nowak M, Malinowski Z, Jozwiak A, Fornal E, Blaszczyk A, Kontek R (2014) Substituted benzoquinazolinones. Part 1: Synthesis of 6-aminobenzo[h] quinazolinones via BuchwaldeHartwig amination from 6-bromobenzo[h] quinazolinones. Tetrahedron 70:5153–5160

    Article  Google Scholar 

  • Panahi F, Yousefi R, Mehraban MH, Nezhad AK (2013) Synthesis of new pyrimidine-fused derivatives as potent and selective antidiabetic α-glucosidase inhibitors. Carbohydr Res 380:81–91

    Article  Google Scholar 

  • Ponnuchamy S, Kanchithalaivan S, Ranjith Kumar R, Ali MA, Choon TS (2014) Antimycobacterial evaluation of novel hybrid arylidene thiazolidine-2,4-diones. Bioorg Med Chem Lett 24:1089–1093

    Article  Google Scholar 

  • Purohit SS, Alman A, Shewale J (2012) Synthesis and antimicrobial activity of a new series of 3,5-disubstitued thiazolidine-2,4-diones. Int J Pharm Pharm Sci 4:273–276

    Google Scholar 

  • Rakowitz D, Maccari R, Ottana R, Vigorita MG (2006) In vitro aldose reductase inhibitory activity of 5-benzyl-2,4-thiazolidinediones. Bioorg Med Chem 14:567–574

    Article  Google Scholar 

  • Seifert A, Ladewig K, Schoherr P, Hofmann K, Lungwitz R, Roth I, Pohlers A, Hoyer W, Baumann G, Schulze S, Hietschold M, Moszner N, Burtscher P, Spange S (2010) Synthesis of dye functionalized xerogels via nucleophilic aromatic substitution of fluoro aromatic compounds with aminosilanes. J Sol-Gel Sci Technol 53:328–341

    Article  Google Scholar 

  • Sunduru N, Srivastava K, Rajakumar S, Puri SK, Saxena JK, Chauhan PMS (2009) Synthesis of novel thiourea, thiazolidinedione and thioparabanic acid derivatives of 4-aminoquinoline as potent antimalarials. Bioorg Med Chem Lett 19:2570–2573

    Article  Google Scholar 

  • Swathi N, Ananda Kumar TD, Subrahmanyam CVS, Satyanarayana K (2013) Synthesis and in silico drug likeness evaluation of N-5-disubstituted-1,3-thiazolidine-2,4-dione analogues. J Pharm Res 6:107–111

    Google Scholar 

  • Wilcox G (2005) Insulin and insulin resistance. Clin Biochem Rev 26:19–39

    Google Scholar 

  • Wu Y, Tai HH, Cho H (2010) Synthesis and SAR of thiazolidinedione derivatives as 15-PGDH inhibitors. Bioorg Med Chem 18:1428–1433

    Article  Google Scholar 

  • Yonemoto R, Shimada M, Gunawan-Puteri MDPT, Kato E, Kawabata J (2014) α-Amylase inhibitory triterpene from abrus precatorius leaves. J Agric Food Chem 62:8411–8414

    Article  Google Scholar 

  • Youssef AM, White MS, Villanueva EB, El-Ashmawy IM, Klegeris A (2010) Synthesis and biological evaluation of novel pyrazolyl-2,4-thiazolidinediones as anti-inflammatory and neuroprotective agents. Bioorg Med Chem 18:2019–2028

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank the management of VIT University, Vellore, for all the support and encouragement. In addition, the support from SIF-Chemistry, School of Advanced Sciences, VIT University, Vellore, and DST-FIST is greatly acknowledged for the spectral analysis.

Author information

Authors and Affiliations

  1. Centre for Organic and Medicinal Chemistry, School of Advanced Sciences, VIT University, Vellore, Tamil Nadu, 632 014, India

    N. Senthilkumar, V. Vijayakumar & S. Sarveswari

  2. Bioinfomatics Division, School of Bioscience and Technology, VIT University, Vellore, Tamil Nadu, 632 014, India

    G. A. Gayathri & M. Gayathri

Authors
  1. N. Senthilkumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. Vijayakumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Sarveswari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. A. Gayathri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Gayathri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Sarveswari.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Senthilkumar, N., Vijayakumar, V., Sarveswari, S. et al. Synthesis of New Thiazolidine-2,-4-dione-azole Derivatives and Evaluation of Their α-Amylase and α-Glucosidase Inhibitory Activity. Iran J Sci Technol Trans Sci 43, 735–745 (2019). https://doi.org/10.1007/s40995-018-0593-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40995-018-0593-x

Keywords

Search

Navigation