Skip to main content
SpringerLink
Log in

Design, Drug-Likeness, Synthesis, Characterization, Antimicrobial Activity, Molecular Docking, and MTT Assessment of 1,3-Thiazolidin-4-one Bearing Piperonal and Pyrimidine Moieties

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

Abstract—

The recent study reported the designing of substituted 3-[4-(1,3-benzodioxol-5-yl)-6-(pyridin-2-yl)pyrimidin-2-yl]-2-(pyridin-2-yl)-1,3-thiazolidin-4-one derivatives and assessed computationally to calculate the bioactivity and physicochemical properties. The substituted 3-[4-(1,3-benzodioxol-5-yl)-6-(pyridin-2-yl)pyrimidin-2-yl]-2-(pyridin-2-yl)-1,3-thiazolidin-4-one derivatives represented the bioactivity score in the zone for an active drug molecule and were in compliance with the Lipinski Rule of five. Then the synthesis, characterization, and biological screening as antimicrobial potential and percent viability of cells were carried out for the substituted 3-[4-(1,3-benzodioxol-5-yl)-6-(pyridin-2-yl)pyrimidin-2-yl]-2-(pyridin-2-yl)-1,3-thiazolidin-4-one derivatives. The zone of inhibition and minimum inhibitory concentration (MIC) findings portrayed that the compounds-(IV) and compound-(V) possessed better antimicrobial activity than the reference drug ciprofloxacin, while the significant antimicrobial potential was observed by other members of the series. The molecular docking studies were performed to assist the in vitro antimicrobial results and the findings exhibited that significant H-bonding in between the substituted 3-[4-(1,3-benzodioxol-5-yl)-6-(pyridin-2-yl)pyrimidin-2-yl]-2-(pyridin-2-yl)-1,3-thiazolidin-4-one derivatives and the residues of GlcN-6-P-synthase, like ASP 474 (I–IX), SER 316 (I–VI), ASN 522 (I–IX), TRP 313 (V) with good binding affinity ranging –7.7 to –6.8 kcal/mole. The compounds represented the less toxic effects to the HepG2 cells and the percent viability of the cells ranging from 93–98%, 73–78% and 70–76% up to 3.125, 50 , 100 mmol/L respectively.

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.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 4.
Fig. 5.

Similar content being viewed by others

REFERENCES

  1. Babu, K.R., Eeshwaraiah, B., Aravind, D., Harshadas, M.M., Rallabaldi, M.R., Apurba, B., and Rakeshwar, B., Monatsh Chem., 2008, vol. 139, pp. 179–181. https://doi.org/10.1007/s00706-007-0772-5

  2. Kulandaivelu, U., Padmini, V.G., Suneetha, K., Shireesha, B., Vidyasagar, J.V., Rao, T.R., Jayaveera, K.N., Basu, A., and Jayaprakash, V., Arch. Pharm., 2011, vol. 344, pp. 84–90. https://doi.org/10.1002/ardp.201000201

  3. Rohit, K., Shabana, I.K., Aparna, B., Mohit, T., and Diwan, S.R., Eur. J. Med. Chem., 2017, vol. 131, pp. 126–140. https://doi.org/10.1016/j.ejmech.2017.03.007

    Article  CAS  Google Scholar 

  4. Hanwen, W., Fei, M., Shuaishuai, N., Feifei, C., Baoli, L., Xiaoxia, Q., Linghao, H., Manjiong, W., Xinyu, Z., Jin, Z., Lefu, L., and Jian, L., Eur. J. Med. Chem., 2018, vol. 145, pp. 235–251. https://doi.org/10.1016/j.ejmech.2017.12.090

    Article  CAS  Google Scholar 

  5. Leite, A.C.L., da Silva, K.P., de Souza, I.A., de Araujo, J.M., and Brondali, D.J., Eur. J. Med. Chem., 2004, vol. 39, pp. 1059–1065. https://doi.org/10.1016/j.ejmech.2004.09.007

  6. Prasanthi, G., Prasad, K.V.S.R.G., and Bharathi, K., Eur. J. Med. Chem., 2013, vol. 66, pp. 516–525. https://doi.org/10.1016/j.ejmech.2013.06.006

    Article  CAS  PubMed  Google Scholar 

  7. Moreira Leal, C., Lopes Pereira, S., Kummerle, A.E., Moreira Leal, D., Tesch, R., de Sant'Anna, C.M.R., Fraga, C.A.M., Barreiro, E.J., Takashi Sudo, R., Zapata-Sudo, G., Eur. J. Med. Chem., 2012, vol. 55, pp. 49–57. https://doi.org/10.1016/j.ejmech.2012.06.056

  8. Arshad, M., Bhat, A.R., Pokharel, S., Ki,m, J-E., Lee, E.J., Athar, F., and Choi, I., Eur. J. Med. Chem., 2014, vol. 71, pp. 229–236. https://doi.org/10.1016/j.ejmech.2013.11.008

    Article  CAS  PubMed  Google Scholar 

  9. Wani, M.Y., Bhat, A.R., Azam, A., Choi, I., and Athar, F., Eur. J. Med. Chem., 2012, vol. 48, pp. 313–320. https://doi.org/10.1016/j.ejmech.2011.12.033

    Article  CAS  PubMed  Google Scholar 

  10. Chavarria, D., Fernandes, C., Silva, V., Silva, C., Gil-Martins, E., Soares, P., Silva, T., Silva, R., Remião, F., Oliveira, P. J., and Borges, F., Eur. J. Med. Chem., 2020, vol. 185, p. 111 770. https://doi.org/10.1016/j.ejmech.2019.111770

    Article  CAS  Google Scholar 

  11. Singh, I.P., Jain, S.K., and Kour, A., Eur. J. Med. Chem., 2010, vol. 4, p. 33.

    Google Scholar 

  12. da Silva Ferreira, W., Freire-de-Lima, L., Barbosa Saraiva, V., Alisson-Silva, F., Mendonca-Previato, L., Previato, J.O., Echevarria, A., and Freire de Lima, M.E. Bioorg. Med. Chem., 2008, vol. 16, pp. 2984–2991.

  13. Gupta, S.D., Rao, G.B., Bommaka, M.K., Raghavendra, N.M., Aleti, S., Arab. J. Chem., 2016, vol. 9, pp. 1878–5352. https://doi.org/10.1016/j.arabjc.2014.08.004

    Article  CAS  Google Scholar 

  14. Wang, S., Bao, L., Song, D., Wang, J., and Cao, X., Bioorg. Med. Chem. Lett., 2019, vol. 29, p. 126 661. https://doi.org/10.1016/j.bmcl.2019.126661

    Article  CAS  Google Scholar 

  15. Brum, J.O.C., Neto, D.C.F., de Almeida, J.S.F.D., Lima, J.A., Kuca, K., França, T.C.C., and Figueroa-Villar, J.D. Int. J. Mol. Sci., 2019, vol. 20, p. 3944. https://doi.org/10.3390/ijms20163944

  16. Arshad, M., J. Iran Chem. Soc., 2020, vol. 17, pp. 1305–1315. https://doi.org/10.1007/s13738-020-01855-9

  17. Ghoneim, A.A., El-Farargy, A.F., Elkanzi, N.A.A. J. Iran Chem. Soc., 2019, vol. 16, pp. 319–325. https://doi.org/10.1007/s13738-019-01768-2

    Article  CAS  Google Scholar 

  18. Hamid, A.M.A., Shehta, W., J. Iran Chem. Soc., 2018, vol. 15, pp. 2771–2779. https://doi.org/10.1007/s13738-018-1464-2

    Article  CAS  Google Scholar 

  19. Bhosle, M.R., Andil, P., Wahul, D., Bondle, G.M., Sarkate, A., Tiwari, S.V., J Iran Chem Soc., 2019, vol. 16, pp. 1553–1561. https://doi.org/10.1007/s13738-019-01633-2

    Article  CAS  Google Scholar 

  20. Ślifirski, G., Król, M., Kleps, J., Podsadni, P., Belka, M., Bączek, T., Siwek, A., Stachowicz, K., Szewczyk, B., Nowak, G., Bojarski, A., Kozioł, A. E., Turło, J., Herold, F., Eur. J. Med. Chem., 2019, vol. 180, pp. 383–397. https://doi.org/10.1016/j.ejmech.2019.07.027

    Article  CAS  PubMed  Google Scholar 

  21. da S. Falcao, E.P., de Melo, S.J., Srivastava, R.M., de A. Catanho, M.T.J., and Do Nascimento, S. C., Eur. J. Med. Chem., 2006, vol. 41, pp. 276–282. https://doi.org/10.1016/j.ejmech.2005.09.009

  22. Kotaiah, Y., Nagaraju, K., Harikrishna, N., Venkata Rao, C., Yamini, L., Vijjulatha, M., Eur. J. Med. Chem., 2014, vol. 75, pp. 195–202. https://doi.org/10.1016/j.ejmech.2014.01.006

    Article  CAS  PubMed  Google Scholar 

  23. Kaur, H., Balzarini, J., Kock, C. de., Smith, P.J., Chibale, K., Singh, K., Eur. J. Med. Chem., 2015, vol. 101, pp. 52–62. https://doi.org/10.1016/j.ejmech.2015.06.024

    Article  CAS  PubMed  Google Scholar 

  24. Maurya, S.S., Bahuguna, A., Khan, S.I., Kumar, D., Kholiya, R., Rawat, D.S., Eur. J. Med. Chem., 2019, vol. 162, pp. 277–289. https://doi.org/10.1016/j.ejmech.2018.11.021

    Article  CAS  PubMed  Google Scholar 

  25. Lee, H.W., Kim, B.Y., Ahn, J.B., Kang, S.K., Lee, J.H., Shin, J.S., Ahn, S.K., Lee, S.J., Yoon, S.S., Eur. J. Med. Chem., 2005, vol. 40, pp. 862–874. https://doi.org/10.1016/j.ejmech.2005.03.019

    Article  CAS  PubMed  Google Scholar 

  26. Verbitskiy, E.V., Cheprakova, E.M., Slepukhin, P.A., Kravchenko, M.A. Skornyakov, S.N., Rusinov, G.L., Chupakhin, O.N., Charushin, V.N., Eur. J. Med. Chem., 2015, vol. 97, pp. 225–234. https://doi.org/10.1016/j.ejmech.2015.05.007

    Article  CAS  PubMed  Google Scholar 

  27. Hafez, H.N., Hussein, H.A.R., El-Gazzar, Abdel-Rahman B.A., Eur. J. Med. Chem., 2010, vol. 45, pp. 4026–4034. https://doi.org/10.1016/j.ejmech.2010.05.060

    Article  CAS  PubMed  Google Scholar 

  28. Zhu, M., Ma, L., Zhou, H., Dong, B., Wang, Y., Wang, Z., Zhou, J., Zhang, G., Wang, J., Liang, C., Cen, S., Wang, Y., Eur. J. Med. Chem., 2020, vol. 185, p. 111 866. https://doi.org/10.1016/j.ejmech.2019.111866

    Article  CAS  Google Scholar 

  29. Keri, R. S., Hosamani, K. M., Shingalapur, R. V., Hugar, M. H., Eur. J. Med. Chem., 2010, vol. 45, pp. 2597–2605. https://doi.org/10.1016/j.ejmech.2010.02.048

    Article  CAS  PubMed  Google Scholar 

  30. Jin, X., Merrett, J., Tong, S., Flower, B., Xie, J., Yu, R., Tian, S., Gao, L., Zhao, J., Wang, X., Jiang, Tao, Proud, C. G., Eur. J. Med. Chem., 2019, vol. 162, pp. 735–751. https://doi.org/10.1016/j.ejmech.2018.10.070

    Article  CAS  PubMed  Google Scholar 

  31. Shehab, W.S., El-Shwiniy, W.H., J. Iran. Chem. Soc., 2018, vol. 15, p. 431. https://doi.org/10.1007/s13738-017-1244-4

    Article  CAS  Google Scholar 

  32. Arshad, M., Khan, M. S., Nami, S. A. A., Ahmad, D., Rus. J. Gen. Chem., 2018, vol. 88, pp. 2154–2162. https://doi.org/10.1134/S1070363218100213

    Article  CAS  Google Scholar 

  33. Carradori, S., Bizzarri, B., D’Ascenzio, M., Monte, C. D., Grande, R., Rivanera, D., Zicari, A., Mari, E., Sabatino, M., Patsilinakos, A., Rino Ragno, R., and Daniela Secci, D., Eur. J. Med. Chem., 2017, vol. 140, pp. 274–292. https://doi.org/10.1016/j.ejmech.2017.09.026

    Article  PubMed  Google Scholar 

  34. Pejović, A., Denić, M.S., Stevanović, D., Damljanović, I., Vukićević, M., Kostova, K., Tavlinova-Kirilova, M., Randjelović, P., Stojanović, N.M., Bogdanović, G.A., Blagojević, P., D’hooghe, M., Radulović, N.S., and Vukićević, R.D., Eur. J. Med. Chem., 2014, vol. 83, pp. 57–73. https://doi.org/10.1016/j.ejmech.2014.05.062

    Article  CAS  PubMed  Google Scholar 

  35. Koppireddi, S., Komsani, J.R., Avula, S., Pombala, S., Vasamsetti, S., Kotamraju, S., and Yadla, R., Eur. J. Med. Chem., 2013, vol. 66, pp. 305–313. https://doi.org/10.1016/j.ejmech.2013.06.005

    Article  CAS  PubMed  Google Scholar 

  36. Rawal, R.K., Tripathi, R., Katti, S.B., Pannecouque, C., and De Clercq, E., Eur. J. Med. Chem., 2008, vol. 43, pp. 2800–2806. https://doi.org/10.1016/j.ejmech.2007.12.015

    Article  CAS  PubMed  Google Scholar 

  37. Raza, S., Srivastava, S.P., Srivastava, D.S., Srivastava, A.K., Haq, W., and Katti, S.B., Eur. J. Med. Chem., vol. 63, 2013, pp. 611–620. https://doi.org/10.1016/j.ejmech.2013.01.054

    Article  CAS  PubMed  Google Scholar 

  38. Revelant, G., Huber-Villaume, S., Dunand, S., Kirsch, G., Schohn, H., and Hesse, S., Eur. J. Med. Chem., 2015, vol. 94, pp. 102–112. https://doi.org/10.1016/j.ejmech.2015.02.053

    Article  CAS  PubMed  Google Scholar 

  39. Barbosa, V.A., Baréa, P., Mazia, R.S., Ueda-Nakamura, T., da Costa, W.F., Foglio, M.A., Ruiz, A.L.T.G., de Carvalho, J.E., Vendramini-Costa, D.B., Nakamura, C., and Sarragiotto, M.H., Eur. J. Med. Chem., 2016, vol. 124, pp. 1093–1104. https://doi.org/10.1016/j.ejmech.2016.10.018

    Article  CAS  Google Scholar 

  40. Trotsko, N., Golus, J., Kazimierczak, P., Paneth, A., Przekora, A., Ginalska, G., and Wujec, M., Eur. J. Med. Chem., 2020, vol. 189, p. 112 045. https://doi.org/10.1016/j.ejmech.2020.112045

    Article  CAS  Google Scholar 

  41. da Silva, D.S., da Silva, C.E.H., Soares, M.S.P., Juliana Hofstatter Azambuja, de Carvalho, T.R., Zimmer, G.C., Frizzo, C.P., Braganhol, E., Spanevello, R.M., and Cunico, W., Eur. J. Med. Chem., 2016, vol. 124, pp. 574–582. https://doi.org/10.1016/j.ejmech.2016.08.057

    Article  CAS  PubMed  Google Scholar 

  42. Alodeani, E.A., Arshad, M., and Izhari, M.A. Asian Pac.J. Health Sci. 2015, vol. 2, pp. 41–47. https://www.apjhs.com/pdf/8-Antileishmanial-screening-physicochemical-properties-and-drug-likeness-of-pyrazole-carbaldehyde-derivatives.pdf.

    Google Scholar 

  43. Alodeani, E.A., Arshad, M., and Izhari, M.A., Eur. J. Pharm. Med. Res., 2015, vol. 2, pp. 324–328. http://www.ejpmr.com/admin/assets/article_issue/ 1448880734.pdf.

    Google Scholar 

  44. Alodeani, E.A., Arshad, M., and Izhari, M.A. Asian Pac. J. Trop. Biomed., 2015, vol. 5, pp. 676–683. https://doi.org/10.1016/j.apjtb.2015.04.010

    Article  CAS  Google Scholar 

  45. Alodeani, E.A., Arshad, M., and Izhari, M.A. Eur. J. Pharm. Med. Res., 2015, vol. 2, pp. 296–301. http://www.ejpmr.com/admin/assets/article_issue/ 1446625932.pdf.

    Google Scholar 

  46. Arshad, M. and Shadab, M., Eur. J. Pharm. Med. Res., 2017, vol. 4, pp. 364–368. http://www.ejpmr.com/ home/abstract_id/2154.

    Google Scholar 

  47. Arshad, M. and Shadab, M., Eur. J. Pharm. Med. Res. 2017, vol. 4, pp. 447–454. https://www.ejpmr.com/home/abstract_id/2267.

    Google Scholar 

  48. Arshad, M., Eur. J. Pharm. Med. Res., 2017, vol. 4, pp. 511–517. http://www.ejpmr.com/admin/assets/article_issue/1512459098.pdf.

    Google Scholar 

  49. Arshad, M., Russ. J. Gen. Chem., 2018, vol. 88, pp. 1886–1891. https://doi.org/10.1134/S1070363218090207

    Article  CAS  Google Scholar 

  50. Arshad, M., Khan, M.S., and Nami, S.A.A., Russ. J. Gen. Chem., 2019, vol. 89, pp. 1851–1858. https://doi.org/10.1134/S1070363219090202

    Article  CAS  Google Scholar 

  51. Arshad, M., Int. J. Pharm. Sci. Res., 2018, vol. 9, pp. 35–41. https://www.ijpsr.info/docs/IJPSR18-09-02-017.pdf.

    CAS  Google Scholar 

  52. Alodeani, E.A., Arshad, M., Izhari, M.A. Europ.J. Biomed. and Pharm. Sci., 2014, vol. 1, pp. 504–527. http://www.ejbps.com/admin/assets/article_issue/ volume_1_december_issue_3/1419598913.pdf.

    Google Scholar 

  53. Arshad, M., Bhat, A.R., Hoi, K.K., Choi, I., and Athar, F, Chin. Chem. Lett., 2017, vol. 28, pp. 1559–1565. https://doi.org/10.1016/j.cclet.2016.12.037

    Article  CAS  Google Scholar 

  54. Arshad, M., Khan, M.S., Nami, S.A.A., and Ahmad, D., SNAppl. Sci., 2019, vol. 1, pp. 1–8. https://doi.org/10.1007/s42452-019-0571-8

    Article  CAS  Google Scholar 

  55. Iram, N.E., Khan, M.S., Jolly, R., Arshad, M., Alam Alam, P., Khan, R.H., and Firdaus, F., J. Photochem. Photobiol. B: Biol., 2015, vol. 153, pp. 20–32. https://doi.org/10.1016/j.jphotobiol.2015.09.001

    Article  CAS  Google Scholar 

  56. Nami, S.A.A., Arshad, M., Shakir, M., Khan, M.S., Alam, M., Lee, D.-U., Park, S., and Sarikavakli, N., Polym. Adv. Technol., 2015, vol. 26, pp. 1627–1638. https://doi.org/10.1002/pat.3591

    Article  CAS  Google Scholar 

  57. Nami, S.A.A., Khan, M.S., Arshad, M., Raza M.A., and Khan, I., Polym. Adv. Technol., 2017, vol. 28, pp. 10–19. https://doi.org/10.1002/pat.3846

    Article  CAS  Google Scholar 

  58. Kareema, A., Laxmi, Arshad M., Nishat, N., J. Photochem. Photobiol. B: Biol., 2016, vol. 160, pp. 163–171. https://doi.org/10.1016/j.jphotobiol.2016.03.030

    Article  CAS  Google Scholar 

  59. Gupta, M.K., Neelakantan, T.V., Sanghamitra, M., Tyagi, R.K., Dinda, A., Maulik, S., Mukhopadhyay, C.K., and Goswami, S.K., Antioxid. Redox Signal., 2006, vol. 8, pp. 1081–1093.

    Article  CAS  Google Scholar 

  60. Mosmann, T., J. Immunol. Methods., 1983, vol. 65, p. 55. https://doi.org/10.1016/0022-1759(83)90303-4

    Article  CAS  PubMed  Google Scholar 

  61. Nayab, P.S., Arif, R, and Arshad, M., Heterocycl.Lett., 2015, vol. 5, pp. 223–239. https://www.heteroletters.org/issue25/PDF/Paper-9.pdf.

    Google Scholar 

  62. Arshad, M., SNAppl. Sci., 2020, vol. 2, p. 467. https://doi.org/10.1007/s42452-020-2243-0

    Article  CAS  Google Scholar 

Download references

ACKNOWLEDGMENTS

The author, Dr. Mohammad Arshad, is highly thankful to the Dean, College of Medicine, Al-Dawadmi, Shaqra University, Kingdom of Saudi Arabia for his cooperation to accomplish this work.

Funding

There was no funding allotted for the study the authors performed the study using their own resources.

Author information

Authors and Affiliations

  1. Department of Basic Sciences, College of Medicine, Al-Dawadmi, Shaqra University, Shaqra, Kingdom of Saudi Arabia

    Mohammad Arshad

Authors
  1. Mohammad Arshad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohammad Arshad.

Ethics declarations

COMPLIANCE WITH ETHICAL STANDARDS

This article does not contain any studies involving animals or human participants performed by any of the authors.

Conflict of Interests

The authors declare that they have no conflict of interest.

Additional information

Corresponding author: phone: +966559712511; e-mail: mohdarshad1985@gmail.com; m.arshad@su.edu.sa.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mohammad Arshad Design, Drug-Likeness, Synthesis, Characterization, Antimicrobial Activity, Molecular Docking, and MTT Assessment of 1,3-Thiazolidin-4-one Bearing Piperonal and Pyrimidine Moieties. Russ J Bioorg Chem 46, 599–611 (2020). https://doi.org/10.1134/S1068162020040056

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1068162020040056

Keywords:

Search

Navigation