Skip to main content
SpringerLink
Log in

Synthesis, Molecular Docking, and Biological Evaluation of the New Hybrids of 4-Thiazolidinone and 4(3H)-Quinazolinone Against Streptozotocin Induced Diabetic Rats

  • Published:
Russian Journal of General Chemistry Aims and scope Submit manuscript

Abstract

A series of new 3-(2-substituted)-4-(oxothiazolidin-3-yl)-2-methylquinazolin-4(3H)-ones 1a–1k is synthesized by using the hybridization approach via one pot multicomponent reaction of 3-amino-2-methylquinazolin-4(3H)-one with substituted benzaldehyde, thioglycolic acid and N, N-dicyclohexylcarbodiimide in DMF media. Structures of the synthesized compounds are elucidated from the spectral data. Antidiabetic activity of the products is tested against streptozotocin induced diabetic rats at a dose of 200 mg/kg compared with standard Pioglitazone (15 mg/kg). Compounds 1b, 1d, 1f, and 1i demonstrate significant antidiabetic activity. Compounds 1b, 1d, 1f, and 1i are evaluated in vitro are tested for serum insulin, cholesterol, triglycerides, total protein, lipoprotein, and enzymes factors. Significant lowering of glycated hemoglobin level is induced by the compounds after 21 days of treatment. Mean±S.E.M. data accumulated are subjected to one-way analysis of variance (ANOVA) followed by Dunnett’s t-test. p < 0.001 was considered statistically significant. Histopathological results accumulated for the rats treated by compounds 1b, 1d and 1f confirm the significant recovery of pancreas destruction. Free energy of binding for all synthesized compounds is calculated using AutoDock 1.5.6 with peroxisome proliferator-activated receptor γ (PPAR γ; PDB ID: 4PRG). Among the synthesized compounds, 1d demonstrates significant binding energy value of −11.46 kcal/mol. The current study is expected to provide useful insight into the design of potential agents that can act as a platform for the development of future antidiabetic drugs.

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

Similar content being viewed by others

References

  1. Deshmukh, A.R., Bhosle, M.R., Khillare, L.D., Dhumal, S.T., Mishra, A., Srivastava, A.K., and Mane, R.A., Res. Med. Intermed., 2017, vol. 43, p. 1107. doi https://doi.org/10.1007/s11164-016-2686-5

    Article  CAS  Google Scholar 

  2. Moller, D.E., Nature, 2001, vol. 414, p. 821. doihttps://doi.org/10.1038/414821a

    Article  CAS  PubMed  Google Scholar 

  3. Sahay, R.K., Reddy, V.S., Bhadada, S.K., Agrawal, J.K., and Agrawal, N.K., J. Indian. Acad. Clin. Med., 2000, vol. 1, p. 245.

    Google Scholar 

  4. Mahapatra, M.K., Saini, R., and Kumar, M., Res. Chem. Intermed., 2016, vol. 42, p. 8239. doi https://doi.org/10.1007/s11164-016-2592-x

    Article  CAS  Google Scholar 

  5. Day, C., Diabet. Med., 1999, vol. 16, p. 179. doi https://doi.org/10.1046/j.1464-5491.1999.00023.x

    Article  CAS  PubMed  Google Scholar 

  6. Kim, B.Y., Ahn, J.B., Lee, H.W., Kang, S.K., Lee, J.H., Shin, J.S., Ahn, S.K., Hong, C I., and Yoon, S.S., Eur. J. Med. Chem., 2004, vol. 39, p. 433. doi https://doi.org/10.1016/j.ejmech.2004.03.001

    Article  CAS  PubMed  Google Scholar 

  7. Laresn, T.M., Toubro, S., and Astrup, A., Int. J. Obes. Relat. Metab. Disord., 2003, vol. 27, p. 147. doi https://doi.org/10.1038/sj.ijo.802223

    Article  CAS  Google Scholar 

  8. Vigorita, M.G., Ottana, R., Monforte, F., Maccari, R., Trovato, A., Monforte, M.T., and Taviano, M.F., Bioorg. Med. Chem. Lett., 2001, vol. 11, p. 2791. doi https://doi.org/10.1016/S0960-894X(01)00476-0

    Article  CAS  PubMed  Google Scholar 

  9. Goel, B., Ram, T., Tyagi, R., Bansal, E., Kumar, A., Mukherjee, D., and Sinha, J.N., Eur. J. Med. Chem., 1999, vol. 34, p. 265. doi https://doi.org/10.1016/S0223-5234(99)80060-9

    Article  CAS  Google Scholar 

  10. Geronikaki, A.A., Pitta, E.P., and Liaras, K.S., Curr. Med. Chem., 2013, vol. 20, p. 4460. doi https://doi.org/10.2174/09298673113209990143

    Article  CAS  PubMed  Google Scholar 

  11. Babaoglu, K., Page, M.A., Jones, V.C., McNeil, M.R., Dong, C., Naismith, J.H., and Lee, R.E., Bioorg. Med. Chem. Lett., 2003, vol. 13, p. 3227. doi https://doi.org/10.1016/S0960-894X(03)00673-5

    Article  CAS  PubMed  Google Scholar 

  12. Dayam, R., Aiello, F., Deng, J., Wu, Y., Garofalo, A., Chen, X., and Neamati, N., J. Med. Chem., 2006, vol. 49, p. 4526. doi https://doi.org/10.1021/jm051296s

    Article  CAS  PubMed  Google Scholar 

  13. Chaudhari, M A., Gujar, J.B., Kawade, D.S., Shinde, P.V., and Shingare, M.S., Res. Chem. Intermed., 2015, vol. 41, p. 10027. doi https://doi.org/10.1007/s11164-015-2010-9

    Article  CAS  Google Scholar 

  14. Maccari, R., Vitale, R.M., Ottana, R., Rocchiccioli, M., Marrazzo, A., Cardile, V., Graziano, A.C., Amodeo, P., Mura, U., and Del Corso, A., Eur. J. Med. Chem., 2014, vol. 81, p. 1. doi https://doi.org/10.1016/j.ejmech.2014.05.003

    Article  CAS  PubMed  Google Scholar 

  15. Archana, Srivastava, V.K. and Kumar, A., Eur. J. Med. Chem., 2002, vol. 37, p. 873. doi https://doi.org/10.1016/S0223-5234(02)01389-2

    Article  CAS  PubMed  Google Scholar 

  16. Chapleo, C.B., Myers, M., Myers, P.L., Saville, J.F., Smith, A.C.B., Stillings, M.R., Tulloch, I.F., Walter, D.S., and Welbourn, A.P., J. Med. Chem., 1986, vol. 29, p. 2273. doi https://doi.org/10.1021/jm00161a024

    Article  CAS  PubMed  Google Scholar 

  17. Srivastava, V K., Archana, and Kumar, A., Bioorg. Med. Chem., 2004, vol. 12, p. 1257. doi https://doi.org/10.1016/j.bmc.2003.08.035

    Article  CAS  PubMed  Google Scholar 

  18. Aziza, M.A., Ibrahim, M.K., and El-Helpy, A.G., Al-Azhar. J. Pharm. Sci., 1994, vol. 14, p. 193.

    CAS  Google Scholar 

  19. Bekhit, A.A. and Khalil, M.A., Pharmazie, 1998, vol. 53, p. 539.

    CAS  PubMed  Google Scholar 

  20. Bedi, P.M.S., Kumar, V., and Mahajan, M.P., Bioorg. Med. Chem. Lett., 2004, vol. 14, p. 5211. doi https://doi.org/10.1016/j.bmcl.2004.07.065

    Article  CAS  PubMed  Google Scholar 

  21. Kung, P.P., Casper, M.D., Cook, K.L., Wilson-Lingardo, L., Risen, L.M., Vickers, T.A., Ranken, R., Blyn, L.B., Wyatt, J.R., Cook, P.D., and Ecker, D.J., J. Med. Chem., 1999, vol. 42, p. 4705. doi https://doi.org/10.1021/jm9903500

    Article  CAS  PubMed  Google Scholar 

  22. Mohamed, M.S., Kamel, M.M., Kassem, E.M., Abotaleb, N., El-moez, S.I.A., and Ahmed, M.F., Eur. J. Med. Chem., 2010, vol. 45, p. 3311. doi https://doi.org/10.1016/j.ejmech.2010.04.014

    Article  CAS  PubMed  Google Scholar 

  23. Ram, V.J., Farhanullah, Tripathi, B.K., and Srivastava, A.K., Bioorg. Med. Chem., 2003, vol. 11, p. 2439. doi https://doi.org/10.1016/S0968-0896(03)00142-1

    Article  CAS  PubMed  Google Scholar 

  24. Kavitha, C.V., Basappa, Swamy, S.N., Mantelingu, K., Doreswamy, S., Sridhar, M.A., Prasad, J.S., and Rangappa, K.S., Bioorg. Med. Chem., 2006, vol. 14, p. 2290. doi https://doi.org/10.1016/j.bmc.2005.11.017

    Article  CAS  PubMed  Google Scholar 

  25. Suthar, S.K., Jaiswal, V., Lohan, S., Bansal, S., Chaudhary, A., Tiwari, A., Alex, A.T., and Joseph, A., Eur. J. Med. Chem., 2013, vol. 63, p. 589. doi https://doi.org/10.1016/j.ejmech.2013.03.011

    Article  CAS  PubMed  Google Scholar 

  26. Lipinski, C.A., Lombardo, F., Dominy, B.W., and Feeney, P.J., Adv. Drug. Deliv. Rev., 2001, vol. 46, p. 3. doi https://doi.org/10.1016/S0169-409X(00)00129-0

    Article  CAS  PubMed  Google Scholar 

  27. Monday, O.M. and Uzoma, A.I., Asian. Pac. J. Trop. Biomed., 2013, vol. 3, p. 628. doi https://doi.org/10.1016/S2221-1691(13)60127-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bala, A., Kar, B., Haldar, P.K., Mazumder, U.K., and Bera, S., J. Ethnopharmacol., 2010, vol. 129, p. 131. doi https://doi.org/10.1016/j.jep.2010.03.010

    Article  PubMed  Google Scholar 

  29. Murtaza, B., Abbas, A., Aslam, A., Akhtar, M.S., Bashir, S., Khalid, M., and Naseer, M.M., Res. Chem. Intermed., 2016, vol. 42, p. 4161. doi https://doi.org/10.1007/s11164-015-2266-0

    Article  CAS  Google Scholar 

  30. Andrarde-Cetto, A., Wiedenfeld, H., J. Ethnopharmacol., 2001, vol. 78, p. 145. doi https://doi.org/10.1016/S0378-8741(01)00335-X

    Article  Google Scholar 

  31. Shirwaikar, A., Rajendran, K., and Barik, R., J. Ethnopharmacol., 2006, vol. 107, p. 285. doi https://doi.org/10.1016/j.jep.2006.03.012

    Article  PubMed  Google Scholar 

  32. Mariappan, G., Saha, B.P., Datta, S., Kumar, D., and Haldar, P.K., J. Chem. Sci., 2011, vol. 123, p. 335. doi https://doi.org/10.1007/s12039-011-0079-2

    Article  CAS  Google Scholar 

  33. Jarrett, R.J., Keen, H., and Hardwick, C., Diabetes, 1970, vol. 19, p. 724. doi https://doi.org/10.2337/diab.19.10.724

    Article  CAS  PubMed  Google Scholar 

  34. Latner, A., Clinical Biochemistry, in Carbohydrate Metabolism: Abnormalities of Post Absorptive Blood Sugar Level, Philadelphia: WB Saunders Co., 1958, p. 48.

    Google Scholar 

  35. Ghosh, S. and Suryawanshi, S.A., Indian. J. Exp. Biol., 2001, vol. 39, p. 748.

    CAS  PubMed  Google Scholar 

  36. Hall, P.M., Cook, J.G., Sheldon, J., Rutherford, S.M., and Gould, B.J., Diabetes Care, 1984, vol. 7, p. 147. doi https://doi.org/10.2337/diacare.7.2.147

    Article  CAS  PubMed  Google Scholar 

  37. Kishore, A., Nampurath, G.K., Mathew, S.P., Zachariah, R.T., Potu, B.K., Rao, M.S., Valiathan, M., and Chamallamudi, M.R., Chem.-Biol. Interaction., 2009, vol. 177, p. 242. doi https://doi.org/10.1016/j.cbi.2008.10.032

    Article  CAS  Google Scholar 

  38. Strate, T., Mann, O., Kleinhans, H., Rusani, S., Schneider, C., Yekebas, E., Freitag, M., Stand, T., Bloechle, C., and Lzbicki, J.R., Pancreas, 2005, vol. 30, p. 254. doi https://doi.org/10.1097/01.mpa.0000157481.22155.2d

    Article  CAS  PubMed  Google Scholar 

  39. Oberfield, J.L., Collins, J.L., Holmes, C.P., Goreham, D.M., Cooper, J.P., Cobb, J.E., Lenhard, J.M., Hull-Ryde, E.A., Mohr, C.P., Blanchard, S.G., Parks, D.J., Moore, L.B., Lehmann, J.M., Plunket, K., Miller, A.B., Milburn, M.V., Kliewer, S.A., and Wilson, T.M., Proc. Natl. Acad. Sci. USA, 1999, vol. 96, p. 6102. doi https://doi.org/10.1073/pnas.96.11.6102

    Article  CAS  PubMed  Google Scholar 

  40. Willson, T.M. and Wahli, W., Curr. Opin. Chem. Biol., 1997, vol. 1, p. 235. doi https://doi.org/10.1016/S1367-5931(97)80015-4

    Article  CAS  PubMed  Google Scholar 

  41. Houssen, M., Shahin, D., Eltoraby, E., and Mesbah, A., Clin. Biochem., 2010, vol. 43, p. 661. doi https://doi.org/10.1016/j.clinbiochem.2010.01.012

    Article  CAS  PubMed  Google Scholar 

  42. Eschwege, E. and Fontbonne, A., Transplant. Proc., 1992, vol. 24, p. 767.

    CAS  PubMed  Google Scholar 

  43. Macdonald, R.P., Standard Methods of Clinical Chemistry, New York: Academic Press, 1970, p. 215.

    Google Scholar 

  44. Balakrishnan, S., Pandhare, R., Malays. J. Pharm. Sci., 2010, vol. 8, p. 13.

    Google Scholar 

  45. Friedewald, W.T., Levy, R.I., and Fredrickson, D.S., Clin. Chem., 1972, vol. 18, p. 499.

    CAS  Google Scholar 

  46. Assmann, G., Schriewer, H., Schmitz, G., and Hagele, E.O., Clin. Chem., 1983, vol. 29, p. 2026.

    CAS  PubMed  Google Scholar 

  47. Donga, S., Shukla, V.J., Ravishankar, B., Ashok, B.K., and Mishtry, I.U., Ayu., 2011, vol. 32, p. 120. doi https://doi.org/10.4103/0974-8520.85743

    Article  PubMed  PubMed Central  Google Scholar 

  48. Kumar, S., Malhotra, R., and Kumar, D., Ind. J. Pharm. Sci., 2010, vol. 72, p. 533. doi https://doi.org/10.4103/0250-474X.73921

    Article  CAS  Google Scholar 

  49. Bonner-Weir, S., Diabetes, 1988, vol. 37, p. 616. doi https://doi.org/10.2337/diab.37.5.616

    Article  CAS  PubMed  Google Scholar 

  50. Masiello, P., Broca, C., Gross, R., Roye, M., Manteghetti, M., Hillaire-Buys, D., Novelli, M., and Ribes, G., Diabetes, 1998, vol. 47, p. 224. doi https://doi.org/10.2337/diab.47.2.224

    Article  CAS  PubMed  Google Scholar 

  51. Sekar, N., Kanthasamy, A., William, S., Subramanian, S., and Govindasamy, S., Pharmacol. Res., 1990, vol. 22, p. 207. doi https://doi.org/10.1016/1043-6618(90)90717-R

    Article  CAS  PubMed  Google Scholar 

  52. Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S., and Olson, A.J., J. Comput. Chem., 2009, vol. 30, p. 2785. doi https://doi.org/10.1002/jcc.21256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Solis, F.J. and Wets, R.J.B., Math. Oper. Res., 1981, vol. 6, p. 19. doi https://doi.org/10.1287/moor.6.1.19

    Article  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge Head, Central Instrumentation Facility (CIF) department, Savitribai Phule Pune University, Pune, India for providing the facilities for Spectral Analysis of compounds.

Author information

Authors and Affiliations

  1. Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Sant Tukaram Nagar, Pimpri, Pune, Maharashtra, 411018, India

    S. S. Jangam

  2. JSPM’s Charak College of Pharmacy and Research, Pune-Nagar Road, Wagholi, Pune, Maharashtra, 412207, India

    S. B. Wankhede

Authors
  1. S. S. Jangam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. B. Wankhede
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. S. Jangam.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jangam, S.S., Wankhede, S.B. Synthesis, Molecular Docking, and Biological Evaluation of the New Hybrids of 4-Thiazolidinone and 4(3H)-Quinazolinone Against Streptozotocin Induced Diabetic Rats. Russ J Gen Chem 89, 1029–1041 (2019). https://doi.org/10.1134/S1070363219050256

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1070363219050256

Keywords

Search

Navigation