Skip to main content

Synthesis, Characterization, Biological, and Molecular Docking Studies of (Z)-N-Substituted-4-(Pyridin-2-yl)-6-(1H-Pyrrolo[2,3-b]Pyridin-4-yl)Pyrimidin-2-Amine

Abstract

A series of fifteen (Z)-N-substituted-4-(pyridin-2-yl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-2-amine, was designed, screened computationally and synthesized. Structures of the compounds (IXV) were elucidated using spectroscopic methods like FT-IR, NMR (1H and 13C), and mass spectroscopy. The compounds were tested for antibacterial and antifungal potential and represented significant antibacterial and antifungal potential. The compounds were also studied for cytotoxicity in terms of percent viability of cells against HepG2 cells and found to be in the range of 70–80% up to 100 µM. The molecular docking was also carried out to observe the formation of H-bond and binding affinities against the receptor GlcN-6P and observed that only the amino acid residues like GLU315, SER316, ASP474, ALA520, and ASN522 were able to form the H-bond with compounds with binding affinity (–8.5 to –6.7 kcal/mol).

This is a preview of subscription content, access via your institution.

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.

REFERENCES

  1. Dighe, S.N.T. and Collet, A., Eur. J. Med. Chem., 2020, vol. 199, pp. 112326–112334. https://doi.org/10.1016/j.ejmech.2020.112326

    CAS  Article  PubMed  Google Scholar 

  2. Zanni, R., Galvez-Llompart, M., Machuca, J., Garcia-Domenech, R., Recacha, E., Pascual, A., Rodriguez-Martinez, J. M., and Galvez, J., Eur. J. Med. Chem., 2017, vol. 137, pp. 233–246. https://doi.org/10.1016/j.ejmech.2017.05.055

    CAS  Article  PubMed  Google Scholar 

  3. Neu, H.C., Science, 1992, vol. 257, pp. 1064–1073. https://doi.org/10.1126/science.257.5073.1064

    CAS  Article  PubMed  Google Scholar 

  4. Pandolfi, F., D’Acierno, F., Bortolami, M., De Vita, D., Gallo, F., De Meo, A., Santo, R R., Costi, D., Simonetti, G., and Scipione, L., Eur. J. Med. Chem., 2019, vol. 65, pp. 93–106. https://doi.org/10.1016/j.ejmech.2019.01.012

    CAS  Article  Google Scholar 

  5. Pingaew, R., Mandi, P., Prachayasittikul, V., Prachayasittikul, S., Ruchirawat, S., and Prachayasittikul, V., Eur. J. Med. Chem., 2018, vol. 143, pp. 1604–1615. https://doi.org/10.1016/j.ejmech.2017.10.057

    CAS  Article  PubMed  Google Scholar 

  6. Li, W., Shuai, W., Sun, H., Xu, F., Bi, Y., Xu, J., Ma, C., Yao, H., Zhu, Z., and Xu, S., Eur. J. Med. Chem., 2019, vol. 163, pp. 428–442. https://doi.org/10.1016/j.ejmech.2018.11.070

    CAS  Article  PubMed  Google Scholar 

  7. Fortes, M.P., Silva, P.B.N.D., Silva, T.G.D., Kaufman, T. S., Militão, G.C.G., and Silveira, C.C., Eur. J. Med. Chem., 2016, vol. 118, pp. 21–26. https://doi.org/10.1016/j.ejmech.2016.04.039

    CAS  Article  PubMed  Google Scholar 

  8. Gupta, S., Maurya, P., Upadhyay, A., Kushwaha, P., Krishna, S., Siddiqi, M.I., Sashidhara, K.V., and B-anerjee, D., Eur. J. Med. Chem., 2018, vol. 143, pp. 1981–1996. https://doi.org/10.1016/j.ejmech.2017.11.015

    CAS  Article  PubMed  Google Scholar 

  9. Singla, R., Gupta, K.B., Upadhyay, S., Dhiman, M., and Jaitak, V., Eur. J. Med. Chem., 2018, vol. 146, pp. 206–219. https://doi.org/10.1016/j.ejmech.2018.01.051

    CAS  Article  PubMed  Google Scholar 

  10. Thokchom, P.S. and Okram, M.S., Mini-Rev. Med. Chem., 2018, vol. 18, pp. 9–25. https://doi.org/10.2174/1389557517666170807123201

    CAS  Article  Google Scholar 

  11. Zarenezhad, E., Farjama, M., and Iraji, A., J. Mol. Struct., 2021, vol. 1230, pp. 129833–129839. https://doi.org/10.1016/j.molstruc.2020.129833

    CAS  Article  Google Scholar 

  12. Balupuri, A., Balasubramanian, P.K., and Joo-Cho, S., Arab. J. Chem., 2020, vol. 13, pp. 1052–1078. https://doi.org/10.1016/j.arabjc.2017.09.009

    CAS  Article  Google Scholar 

  13. Bhalgat, C.M., Ali, M.I., Ramesh, B., and Ramu, G., Arab. J. Chem., 2014, vol. 7, pp. 986–983. https://doi.org/10.1016/j.arabjc.2010.12.021

    CAS  Article  Google Scholar 

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

    CAS  Article  PubMed  Google Scholar 

  15. Liu, P., Yang, Y., Tang, Y., Yang, T., Sang, Z., Liu, Z., Zhang, T., and Luo, Y., Eur. J. Med. Chem., 2019, vol. 163, pp. 169–182. https://doi.org/10.1016/j.ejmech.2018.11.054

    CAS  Article  PubMed  Google Scholar 

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

    CAS  Article  PubMed  Google Scholar 

  17. Chopra, R., Chibale, K., and Singh, K., Eur. J. Med. Chem., 2018, vol. 148, pp. 39–53. https://doi.org/10.1016/j.ejmech.2018.02.021

    CAS  Article  PubMed  Google Scholar 

  18. Tuo, W., Bollier, M., Leleu-Chavain, N., Lemaire, L., Barczyk, A., Dezitter, X., Klupsch, F., Szczepanski, F., Spencer, J., Chavatte, P., and Millet, R., Eur. J. Med. Chem., 2018, vol. 146, pp. 68–78. https://doi.org/10.1016/j.ejmech.2018.01.034

    CAS  Article  PubMed  Google Scholar 

  19. Federico, S., Margiotta, E., Salmaso, V., Pastorin, G., Kachler, S., Klotz, K.-N., Moro, S., and Spalluto, G., Eur. J. Med. Chem., 2018, vol. 157, pp. 837–851. https://doi.org/10.1016/j.ejmech.2018.08.042

    CAS  Article  PubMed  Google Scholar 

  20. Li, Z.H., Liu, X.Q., Geng, P.F., Suo, F.Z., Ma, J.L., Yu, B., Zhao, T.Q., Zhou, Z.Q., Huang, C.X.  Zheng, Y.C., and Liu, H.M., ACS Med. Chem. Lett., 2017, vol. 8, pp. 384–389. https://doi.org/10.1021/acsmedchemlett.6b00423

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. Zhang, X., Li, X., Li, D., Qu, G., Wang, J., Loiseau, P.M., and Fan, X., Bioorg. Med. Chem. Lett., 2009, vol. 19, pp. 6280–6283. https://doi.org/10.1016/j.bmcl.2009.09.101

    CAS  Article  PubMed  Google Scholar 

  22. Antre, R.V., Cendilkumar, A., Goli, D., Andhale, G.S., and Oswal, R.J., Saudi Pharm. J., 2011, vol. 19, pp. 233–243. https://doi.org/10.1016/j.jsps.2011.05.006

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Fang, Y., Xiong, L., Hu, J., Zhang, S., Xie, S., Tu, L., Wan, Y., Jin, Y., Li, X., Hu, S., and Yang, Z., Bioorg. Chem., 2019, vol. 86, pp. 103–111. https://doi.org/10.1016/j.bioorg.2019.01.032

    CAS  Article  PubMed  Google Scholar 

  24. Molinari, A., Lucia-Fallacara, A., Di-Maria, S., Zamperini, C., Poggialini, F., Musumeci, F., Schenone, S., Angelucci, A., Colapietro, A., Crespan, E., Kissova, M., Maga, G., and Botta, M., Bioorg. Med. Chem. Lett., 2018, vol. 28, pp. 3454–3457. https://doi.org/10.1016/j.bmcl.2018.09.024

    CAS  Article  PubMed  Google Scholar 

  25. Bhosle, M.R., Deshmukh, A.R., Pal, S., Srivastava, A.K., and Mane, R.A. Bioorg. Med. Chem. Lett., 2015, vol. 25, pp. 2442–2446. https://doi.org/10.1016/j.bmcl.2015.03.068

    CAS  Article  PubMed  Google Scholar 

  26. Alzahrani, K.J., Matyugina, E.S., Khandazhinskaya, A.L., Kochetkov, S.N., Radtke, K.L.S., and de Koning, H.P., Bioorg. Med. Chem. Lett., 2017, vol. 27, pp. 3081–3086. https://doi.org/10.1016/j.bmcl.2017.05.052

    CAS  Article  PubMed  Google Scholar 

  27. Jiang, J.-K., Huang, X., Shamim, K., Patel, P.R., Lee, A., Wang, A.Q., Nguyen, K., Tawa, G., Cuny, G.D., Yu, P.B., Zheng, W., Xu, X., Sanderson, P., and Huang, W., Bioorg. Med. Chem. Lett., 2018, vol. 28, pp. 3356–3362. https://dx.doi.org/10.1016%2Fj.bmcl.2018.09.006

    CAS  Article  Google Scholar 

  28. Alzahrani, K.J.H., Ali, J.A.M., Eze, A.A., Looi, W.L., Tagoe, D.N.A., Creek, D.J., Barrett, M.P., and de Koning, H.P., Int. J. Parasitol. Drugs Drug Resist., 2017, vol. 7, pp. 206–226. https://doi.org/10.1016/j.ijpddr.2017.04.003

    Article  PubMed  PubMed Central  Google Scholar 

  29. Sun, W., Hu, S., Fang, S., and Yan, H., Bioorg. Chem., 2019, vol. 78, pp. 103232–103239. https://doi.org/10.1016/j.bioorg.2019.103232

    CAS  Article  Google Scholar 

  30. Li, G., Zhang, X., Huang, J., Li, T., Yang, S., Wang, Y., Jiang, J., Xia, B., Chen, M., and Dong, W., Chem. Engineer. J., 2022, vol. 435, p. 134766. https://doi.org/10.1016/j.cej.2022.134766

    CAS  Article  Google Scholar 

  31. Arshad, M., SN Appl. Sci., 2020, vol. 2, pp. 467–475. https://doi.org/10.1007/s42452-020-2243-0

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  33. Arshad, M., Khan, M.S., and Nami, SAA., J. Iran. Chem. Soc., 2021, vol. 18, pp. 2397–2406. https://doi.org/10.1007/s13738-021-02200-4

    CAS  Article  Google Scholar 

  34. Arshad, M., Russ. J. Bioorg. Chem., 2020, vol. 46, pp. 599–611. https://doi.org/10.1134/S1068162020040056

    Article  Google Scholar 

  35. Arshad, M., Ahmad, D., and Akhter, R., Chem. Data Collect., 2020, vol. 28, pp. 100405–10415. https://doi.org/10.1016/j.cdc.2020.100405

    CAS  Article  Google Scholar 

  36. Arshad, M., Khan, M.S., Nami, SAA., Ahmad, S. I., Kashif, M., and Anjum, A., J. Iran. Chem. Soc., 2021, vol. 18, pp. 1713–1727, https://doi.org/10.1007/s13738-020-02144-1

    CAS  Article  Google Scholar 

  37. 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

    CAS  Article  Google Scholar 

  38. Arshad, M., Khan, M.S., and Nami, S.A.A., SN Appl. Sci., 2019, vol. 1, pp. 548–556. https://doi.org/10.1007/s42452-019-0571-8

    CAS  Article  Google Scholar 

  39. Chaban, T., Horishny, V., Arshad, M., Chulovska, Z., Kostyshyn, L., Drapak, I., and Matiychuk, V., Biointerface Res. Appl. Chem., 2021, vol. 11, pp. 12434–12446. https://doi.org/10.33263/BRIAC114.1243412446

    CAS  Article  Google Scholar 

  40. Chaban, T., Arshad, M., Kostyshyn, L., Drapak, I., and Matiychuk, V., Eur. Chem. Bull., 2021, vol. 10, pp. 230–236. https://doi.org/10.17628/ECB.2021.10.230-236

    CAS  Article  Google Scholar 

  41. Arshad, M., Beg, M.A., Bhat, A.R., and Athar, F., Indian J. Chem. (Section B), 2021, vol. 2021, pp. 1636–1651. http://nopr.niscair.res.in/handle/123456789/58610

  42. Alodeani, E.A., Izhari, M.A., and Arshad, M., Asian Pac. J. Health Sci., 2015, vol. 2, pp. 41–47. https://doi.org/10.21276/apjhs.2015.2.2.8

    Article  Google Scholar 

  43. Bhat A.R., Arshad M., Lee, E.J., Pokharel, S., Choi, I., and Athar, F., Chem. Biodiv., 2013, vol. 10, pp. 2267–2277. https://doi.org/10.1002/cbdv.201300009

    CAS  Article  Google Scholar 

  44. 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

    CAS  Article  Google Scholar 

  45. Arshad, M., Bhat, A.R., Pokharel, S., Kim, 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

    CAS  Article  PubMed  Google Scholar 

  46. Rollas, S., Gulerman, N., and Erdeniz, H., Il Farmaco, 2002, vol. 57, pp. 171–174. https://doi.org/10.1016/s0014-827x(01)01192-2

    CAS  Article  PubMed  Google Scholar 

  47. Arshad, M., Int. J. Pharm. Sci. Res., 2014, vol. 5, pp. 1024–1037. https://doi.org/10.13040/IJPSR.0975-8232.5(4).1000-13

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  50. Kareem, A., Laxmi, Arshad, M., Nami S.A.A., and Nishat, N., J. Photochem. Photobiol. B: Biology, 2016, vol. 160, pp. 163–171. https://doi.org/10.1016/j.jphotobiol.2016.03.030

    CAS  Article  PubMed  Google Scholar 

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

    CAS  Article  PubMed  Google Scholar 

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

    CAS  Article  Google Scholar 

  53. Bushra, R., Shahadat, M., Khan, M.A., Adnan, R., Arshad, M., Rafatullah M., Naushad, M., Int. J. Env. Sci. Technol., 2015, vol. 12, pp. 3635–3642. https://doi.org/10.1007/s13762-014-0726-5

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  55. Khan, Z.K., Proceedings of the International Workshop UNIDO-CDRI, 1997, p. 210.

  56. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically Approved Standard, 11th ed. CLSI document M7-A7. Wayne, Pennsylvania, USA, 2006, pp. 1–49. https://clsi.org/media/ 1928/m07ed11_sample.pdf

  57. Gupta, M.K., Neelakantan, T.V., Sanghamitra, M., Tyagi, RK., Dinda, A., Maulik, S., Mukhopadhyay, C.K., and Goswami, S.K., Antioxid. Redox Signal., 2006, vol. 8, pp. 1081–1093. https://doi.org/10.1089/ars.2006.8.1081

    CAS  Article  PubMed  Google Scholar 

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

    CAS  Article  PubMed  Google Scholar 

  59. Mouilleron S., Badet-Denisot M.A., and Golinelli-Pimpaneau B., J. Mol. Biol., 2008, vol. 377, pp. 1174–1185. https://doi.org/10.1016/j.jmb.2008.01.077

    CAS  Article  PubMed  Google Scholar 

  60. Trott, O. and Olson A.J., J. Comput. Chem., 2010, vol. 31, pp. 455–461. https://dx.doi.org/10.1002%2Fjcc.21334

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

ACKNOWLEDGMENTS

Dr. Mohammad Arshad is highly thankful to the deanship of scientific research, Shaqra University, Kingdom of Saudi Arabia, for the successful accomplishment of this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Arshad.

Ethics declarations

COMPLIANCE WITH ETHICAL STANDARDS

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

Conflict of Interest

The authors declare that they have no conflicts of interest.

Additional information

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1134/S1068162022050065.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Arshad, M., Akhter, M.S. Synthesis, Characterization, Biological, and Molecular Docking Studies of (Z)-N-Substituted-4-(Pyridin-2-yl)-6-(1H-Pyrrolo[2,3-b]Pyridin-4-yl)Pyrimidin-2-Amine. Russ J Bioorg Chem 48, 1068–1075 (2022). https://doi.org/10.1134/S1068162022050065

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1068162022050065

Keywords:

  • pyrimidine
  • indole
  • antimicrobial
  • MTT assay
  • molecular docking