Skip to main content
SpringerLink
Log in

New Diclofenac Derivatives as Anti-Microbial, Anti-Inflammatory Agents: Design, Synthesis, Biological Screening, and Molecular Docking Study

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

Abstract

Diclofenac is considered one of the best drugs used as anti-inflammatory agent, so in the present work new diclofenac derivatives containing bioactive moieties, such as triazole, oxadiazole, and thiadiazol, were synthesized. The structures of the new compounds were established based on spectral and elemental analysis. The new synthesized compounds were tested against anti-inflammatory agents and exhibited high activity as expected. The binding position of new diclofenac derivatives toward Cox-1 and Cox-2 enzymes was proved by molecular docking. Also, some of the new compounds were tested against bacteria and displayed high activity.

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.

Similar content being viewed by others

REFERENCES

  1. Kakehashi, S., Stanley, H.R., and Fitzgerald, R.J., Oral Surg. Oral Med. Oral Pathol., 1965, vol. 20, pp. 340–349. https://doi.org/10.1016/0030-4220(65)90166-0

    Article  CAS  PubMed  Google Scholar 

  2. Rani Basu, L., Mazumdar, K., Dutta, N.K., Karak, P., and Dastidar, S.G., Microbiol. Res., 2005, vol. 160, pp. 95–100.https://doi.org/10.1016/j.micres.2004.10.002

    Article  CAS  PubMed  Google Scholar 

  3. Hendricks, O., Butterworth, T.S., Kristiansen, J.E., Int. J. Antimicrob. Agents, 2003, vol. 22, pp. 262–264. https://doi.org/10.1016/s0924-8579(03)00205-x

    Article  CAS  PubMed  Google Scholar 

  4. Dastidar, S.G.,Chaudhury, A.S., Annadurai, S., Mookerjee, M., and Chakrabarty, A.N.,  J. Chemother., 1995, vol. 7, pp. 201–206. https://doi.org/10.1179/joc.1995.7.3.201

    Article  CAS  PubMed  Google Scholar 

  5. Dastidar, S.G., Ganguly, K., Chaudhuri, K., and Chakrabarty, A.N., Int. J. Antimicrob. Agents, 2000, vol. 14, pp. 249–251. https://doi.org/10.1016/s0924-8579(99)00159-4

    Article  CAS  PubMed  Google Scholar 

  6. Wang, W.H.,Wong, W.M., Dailidiene, D., Berg, D.E., Gu, Q., and Lai, K.C., Gut, 2003, vol. 52, pp. 490–495. https://doi.org/10.1136/gut.52.4.490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Patil, R.B., Nagaraj, T., and Patel,V.B., J. Contemp. Dent. Pract., 2012, vol. 13, pp.749–752. https://doi.org/10.5005/jp-journals-10024-1222

    Article  PubMed  Google Scholar 

  8. Salem-Milani, A., Balaei-Gajan, E., Rahimi, S., Moosavi, Z., Abdollahi, A., Zakeri-Milani, P., and Bolourian, M., J. Dent. (Tehran), 2013, vol. 10, pp.16–22. doi.org/PMC3666061/J Dent 23724199

  9. Dutta, N.K., Mazumdar, K., Seok, S.H., and Park, J.H., Lett. Appl. Microbiol., 2008, vol. 47, pp. 106–111. https://doi.org/10.1111/j.1472-765x.2008.02391.x

    Article  CAS  PubMed  Google Scholar 

  10. Dutta, N.K., Mazumdar, K.,Dastidar, S.G., and Park, J.H., Int. J. Antimicrob. Agents, 2007, vol. 30, pp. 336–340. https://doi.org/10.1016/j.ijantimicag.2007.04.016

    Article  CAS  PubMed  Google Scholar 

  11. Dutta, N.K., Mazumdar, K., Dastidar, S.G., and Kumar, K.A., Biol. Pharm. Bull., 2005, vol. 28, pp. 713– 717. https://doi.org/10.1248/bpb.28.713

    Article  PubMed  Google Scholar 

  12. Alqahtani, F.Y., Aleanizy, F.S., El Tahir, E., Alquadeib, B.T., Alsarra, I.A., Alanazi, J.S., and Abdelhady, H.G., Saudi Pharm. J., 2019, vol. 27, pp. 82–87. https://doi.org/10.1016/j.jsps.2018.08.001

    Article  PubMed  Google Scholar 

  13. Kumar, R.S., Arif, I.A., Ahamed, A., and Idhayadhulla, A., Saudi J. Biol. Sci., 2016, vol. 23, pp. 614–620. https://doi.org/10.1016/j.sjbs.2015.07.005

    Article  CAS  Google Scholar 

  14. Chockattu, S.J., Deepak, B.S., and Goud, K.M., J. Conserv. Dent., 2017, vol. 20, pp. 80–84. https://doi.org/10.4103/0972-0707.209079

    Article  CAS  Google Scholar 

  15. Lagadinou, M., Onisor, M.O., Rigas, A., Musetescu, D.V., Gkentzi, D., Assimakopoulos, S.F., Panos, G., and Marangos, M., Antibiotics, 2020, vol. 9, pp. 107–113. https://doi.org/10.3390/antibiotics9030107

    Article  CAS  PubMed Central  Google Scholar 

  16. Buyukkurt, M.C., Gungormus M., and Kaya, O., J. Oral Maxillofac. Surg., 2006, vol. 64, pp. 1761–1766. https://doi.org/10.1016/j.joms.2005.11.107

    Article  PubMed  Google Scholar 

  17. Spivakovsky, S., J. Evid. Based Dent. Pract., 2012, vol. 13, pp. 105–107. https://doi.org/10.1038/sj.ebd.6400889

    Article  Google Scholar 

  18. Negm, M.M., Oral Surg. Oral Med. Oral Pathol., 1994, vol. 77, pp. 507–513. https://doi.org/10.1016/0030-4220(94)90233-x

    Article  CAS  PubMed  Google Scholar 

  19. Kristiansen, J.E., Hendricks, O., Delvin, T.,Butterworth, T.S., Aagaard, L., and Christensen, J.B., J. Antimicrob. Chemother., 2007, vol. 59, pp. 1271–1279. https://doi.org/10.1093/jac/dkm071

    Article  CAS  PubMed  Google Scholar 

  20. Palomer, A., Cabre, F., Pascual, J., Campos, J., Trugillo, M.A., Entrena, A., Gallo, M.A., Garcia, L., Maclcon, D., and Espinosa., A., J. Med. Chem., 2002, vol. 45, pp. 1402–1411. https://doi.org/10.1021/jm010458r

    Article  CAS  PubMed  Google Scholar 

  21. Mehanna, S.A., Am. J. Pharm. Educ., 2003, vol. 67, pp. 63–72. https://doi.org/10.5688/aj670263

    Article  Google Scholar 

  22. Dutta, N.K., Annadurai, S., Mazumdar, K.,Dastidar, S.G.,Kristiansen, J.E., and Molnar, J., Int. J. Antimicrob. Agents, 2007, vol. 30, pp. 242–249. https://doi.org/10.1016/j.ijantimicag.2007.04.018

    Article  CAS  PubMed  Google Scholar 

  23. Hamberg, M., Svensson, J., and Samuelsson, B., Proc. Natl. Acad. Sci. U. S. A., 1974, vol. 71, pp. 3824–3828. https://doi.org/10.1073/pnas.71.10.3824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hampannavar, M.K. and Palkar, G.A., Indian J. Health Sci. Biomed. Res., 2019, vol. 12, pp. 35–43. https://doi.org/10.4103/kleuhsj.kleuhsj_151_18

    Article  Google Scholar 

  25. Souza, R.D. and Chattree, A., Chem. Sci. Trans., 2015, vol. 4, pp. 208–212. https://doi.org/10.7598/cst2015.928

    Article  CAS  Google Scholar 

  26. Noolvi, M.N., Patel, H.M., and Kamboj, S., Arab. J. Chem., 2016, vol. 9, pp. S1283–S1289. https://doi.org/10.1016/j.arabjc.2012.02.003

    Article  CAS  Google Scholar 

  27. Bhandari, V.S., Bothara, G.K., Raut, K.M., A. Ajit Patil, P., Aniket, S., and Mokale., J.V., Bioorg. Med. Chem., 2008, vol. 16, pp. 1822–1831. https://doi.org/10.1016/j.bmc.2007.11.014

    Article  CAS  PubMed  Google Scholar 

  28. Shaikh, A. and Meshram, J., J. Heterocycl. Chem., 2016, vol. 53, pp. 1176–1182. https://doi.org/10.1002/jhet.2377

    Article  CAS  Google Scholar 

  29. Lamani, R.S., Shetty, N.S., Kamble, R.R., and Khazi, I.A., Eur. J. Med. Chem., 2009, vol. 44, pp. 2828–2833. https://doi.org/10.1016/j.ejmech.2008.12.019

    Article  CAS  PubMed  Google Scholar 

  30. Yusuf, M., Solanki, I., and Jain, P., Chem. Sci., 2012, vol. 124, pp.703–704. https://doi.org/10.1007/s12039-012-0247-z

    Article  CAS  Google Scholar 

  31. Palkar, M.B., Singhai, A.S., Ronad, P.M., Vishwanathswamy, A.H., Boreddy, T.S., Veerapur, V.P., Shaikh, M.S., Rane, R.A., and Karpoormath, R., Bioorg. Med. Chem., 2014, vol. 22, pp. 2855–2866. https://doi.org/10.1016/j.bmc.2014.03.043

    Article  CAS  PubMed  Google Scholar 

  32. Ingale, N., Maddi, V.S., Palkar, M.B., Ronad, P.M., Mamledesai, S.N., and Vishwanathswamy, A.H., Med. Chem. Res., 2012, vol. 21, pp. 16–26. https://doi.org/10.1007/s00044-010-9494-z

    Article  CAS  Google Scholar 

  33. Abdelgawad, M.A., Labib, M.B., Ali, W., Kamel, G., Azouz, A.A., and El-Nahass, E.S., Bioorg. Chem., 2018, vol. 78, pp. 103–114. https://doi.org/10.1016/j.bioorg.2018.03.011

    Article  CAS  PubMed  Google Scholar 

  34. Ibrahim, M.M., Elsaman, T., and Al-Nour, M.Y., Int. J. Med. Chem., 2018, vol. 2018, pp. 1–11. https://doi.org/10.1155/2018/9139786

    Article  Google Scholar 

  35. Banerjee, A.G., Das, N., Shengule, S.A., Shrivastava, R.S., and Srivastava, S.K., Eur. J. Med. Chem., 2015, vol. 101, pp. 81–95. https://doi.org/10.1016/j.ejmech.2015.06.020

    Article  CAS  PubMed  Google Scholar 

  36. Tolba, M.S., Kamal El-Dean, A.M., Ahmed, M., Hassanien, R., and Farouk, M., Arkivoc, 2017, vol. 5, pp. 229–243. https://doi.org/10.24820/ark.5550190.p010.226

    Article  CAS  Google Scholar 

  37. Tolba, M.S., Kamal El-Dean, A.M., Ahmed, M., Hassanien, R., and Farouk, M., J. Heterocyclic Chem., 2018, vol. 55, pp. 408–418. https://doi.org/10.1002/jhet.3056

    Article  CAS  Google Scholar 

  38. Saddik, A.A., Kamal El-Dean, A.M., El-Said, W.A., Hassan, K.M., and Abbady, M.S., J. Heterocyclic Chem., 2018, vol. 55, pp. 2111–2122. https://doi.org/10.1002/jhet.3256

    Article  CAS  Google Scholar 

  39. Sayed, M., Younis, O.,Hassanien, R., Ahmed, M., Mohammed, A.A.K., and Kamal El-Dean, A.M., J. Photochem. Photobiol. A Chem., 2019, vol. 383, pp. 111 969–111 979. https://doi.org/10.1016/j.jphotochem.2019.111969

    Article  CAS  Google Scholar 

  40. Kamal El-Dean, A.M., Abd-Ella, A.A.,Hassanien, R., El-Sayed, M.E.A., Zaki, R.M., and Abdel Raheem, Sh.A.A., Toxicol. Rep., 2018, vol. 6, pp. 100–104.https://doi.org/10.1016/j.toxrep.2018.12.004

    Article  CAS  Google Scholar 

  41. Sivaraj, S., Muthumani, P., Venkataraman, S., Raamamurthy, J., Siva Kumar, R., and Kumarnallasivan, P., Pharma Chem., 2012, vol. 3, pp. 1339–1349.

    Google Scholar 

  42. Yaseen, Y.S., Farhan, M.S., and Salih, S.J., Pharma Chem., 2017, vol. 9, pp. 44–49.

    CAS  Google Scholar 

  43. Abbas, S.E., Abou-Youssef, H.E., El-Taliaw, G.M., and Hassan, A.B., Egypt. J. Pharm. Sci., 1991, vol. 32, pp. 503–514.

    CAS  Google Scholar 

  44. Palled, M.S. and Dushyanth, R.V., World J. Pharm. Res., 2016, vol. 5, pp. 242–252. https://doi.org/10.20959/wjpr201612-7386

    Article  CAS  Google Scholar 

  45. Kendre, D.B., Toche, R.B., and Jachak, M.N., J. Heterocycl Chem., 2008, vol. 45, pp. 1281–1286. https://doi.org/10.1002/jhet.5570450504

    Article  CAS  Google Scholar 

  46. Winter, C.A., Risley, E.A., and Nuss, G.W., Proc. Soc. Exp. Biol. Med., 1962, vol. 111, pp. 544–547. https://doi.org/10.3181/00379727-111-27849

    Article  CAS  PubMed  Google Scholar 

  47. Molecular Operating Environment (MOE) (2014).0901, Chemical Computing Group Inc., 1010, Sherbooke St. West, Suite #910, Montreal, QC, Canada, H3A2R7, 2016.

  48. Orlando, B.J. and Malkowski, M. G., Acta Crystallogr. Sect. F Struct. Biol. Commun., 2016, vol. 72, pp. 772–776. https://doi.org/10.1107/s2053230x16014230

    Article  CAS  Google Scholar 

  49. GraphPad Prismv 5. https://www.graphpad.com. https://doi.org/10.1086/419365

  50. Nargund, L.V.G., Reddy, G.R.N., and Hariprasad, V., J. Pharm Sci., 1994, vol. 83, pp. 246–248. https://doi.org/10.1002/jps.2600830226

    Article  CAS  PubMed  Google Scholar 

Download references

ACKNOWLEDGMENTS

The authors are very grateful to Mr. Abdelreheem Abdelfattah Saddik, assistant lecturer, Department of Chemistry, Faculty of Science, Assiut University for your contributions in the study of some of my samples (13C, 1H-NMR) at Materials Science and Technology Department, National Chiao Tung University, Taiwan. I also thank Dr. Mostafa Ahmed, assistant professor, Department of Chemistry, Faculty of Science, New Valley University for his constant efforts and his view Constructive during the course of the preparation of the manuscript We also take this opportunity to thank Dr. Omneya Ahmed Ibrahim Faculty of Pharmacy, Assiut University, particularly in the field of molecular docking research, with many thanks.

Author information

Authors and Affiliations

  1. Chemistry Department, Faculty of Science, Assiut University, 71516, Assiut, Egypt

    Mahmoud M. Hamed, Adel M. Kamal El-Dean & Shawkat A. Abdel-Mohsen

  2. Chemistry Department, Faculty of Science, New Valley University, 72511, El-Kharja, Egypt

    Mahmoud S. Tolba

Authors
  1. Mahmoud M. Hamed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adel M. Kamal El-Dean
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shawkat A. Abdel-Mohsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mahmoud S. Tolba
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mahmoud S. Tolba.

Ethics declarations

COMPLIANCE WITH ETHICAL STANDARDS

This article does not contain any studies involving human participants performed by any of the authors. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Conflict of Interests

The authors declare that they have no conflicting financial interest.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mahmoud M. Hamed, El-Dean, A.M., Abdel-Mohsen, S.A. et al. New Diclofenac Derivatives as Anti-Microbial, Anti-Inflammatory Agents: Design, Synthesis, Biological Screening, and Molecular Docking Study. Russ J Bioorg Chem 47, 208–220 (2021). https://doi.org/10.1134/S1068162021010088

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1068162021010088

Keywords:

Search

Navigation