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Indian Journal of Pharmaceutical Education and ResearchNOW IN
Article

Synthesis and Biological Evaluation of 5,6-Dimethylthieno[2,3-d]Pyrimidin-4(3H)-One Derivatives as Selective Cyclooxygenase 2 Inhibitors

Lim Tse Mun1, Jamie Kow Kean Hing1, Pran Kishore Deb2★, Katharigatta Narayanaswamy Venugopala3,4, Raghu Prasad Mailavaram5, Ammena Yahia Binsaleh6, Sireen Abdul Rahim Shilbayeh6★ Corresponding author

  1. 1Department of Pharmaceutical Sciences, School of Pharmacy, International Medical University, Kuala Lumpur,MALAYSIA.
  2. 2Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology (BIT), Mesra, Ranchi, Jharkhand, INDIA.
  3. 3Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, SAUDI ARABIA.
  4. 4Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, Durban, SOUTH AFRICA.
  5. 5Department of Pharmaceutical Chemistry, Shri Vile Parle Kelavani Mandal’s Institute of Pharmacy, Samtanagar, Dhule, Maharashtra, INDIA.
  6. 6Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, SAUDI ARABIA.

CORRESPONDENCE

Pran Kishore Deb

Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology (BIT), Mesra, Ranchi-835215, Jharkhand, INDIA. ; prankishoredeb@bitmesra.ac.in

prankishore1@gmail.com

ORCID: 0000-0002-8650-2874

Received: 12-11-2023; Revised: 14-01-2024; Accepted: 19-03-2024.

Volume 58, Issue 2S · pp. s515–s520 · PUBLISHED Apr-Jun 2024 · DOI: 10.5530/ijper.58.2s.53

View on IJPER original site ↗

ABSTRACT

Background NSAIDs are well-established for treating pain, fever, and inflammation mainly by inhibiting inducible Cyclooxygenase 2 (COX-2) isoenzyme. However, most of the marketed NSAIDs non-selectively inhibit physiological COX-1 and exhibit adverse side effects like GI ulcers, renal toxicity, and platelet disorder. Moreover, cardiac side effects also led to the market withdrawal of some of the potential selective COX-2 inhibitors. Thus, several investigations are underway by researchers from academia and industry in search of safer and more effective COX-2 selective inhibitors devoid of existing side effects. Materials and Methods In this work, four 2-substituted-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one derivatives (5,6,7,8 and 9) have been synthesized, purified, and characterized based on their physical and spectral data. These compounds were evaluated (in vitro) for their affinity and selectivity for human COX-2 enzyme against COX-1 isoenzyme using indomethacin as a positive control. Results and Discussion Compound 5 with para fluorophenyl substituent was found to be the most potent, exhibiting better inhibition and selectivity towards COX-2 isoenzyme (IC50=42.19 M, SI=4.81) against COX-1 isoenzyme (IC50=202.96 M, SI=4.81) as compared to the other derivatives (6-8). Conclusion: The activity of compound 5 is promising compared to the non-selective drug indomethacin (IC50 COX-1=0.68 M, COX-2=18.3 M, SI=0.04). Therefore, compound 8 can be considered a lead molecule for further optimization to develop novel selective COX-2 inhibitors at nanomolar potency.

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    Mun, L. T., Hing, J. K. K., Deb, P. K., Venugopala, K. N., Mailavaram, R. P., Binsaleh, A. Y., & Shilbayeh, S. A. R. (2024). Synthesis and Biological Evaluation of 5,6-Dimethylthieno[2,3-d]Pyrimidin-4(3H)-One Derivatives as Selective Cyclooxygenase 2 Inhibitors. Indian Journal of Pharmaceutical Education and Research, 58(2S), s515–s520. https://doi.org/10.5530/ijper.58.2s.53