Synthesis, molecular docking study, and in vivo biological evaluation of pyrazolopyridines derived from monocarbonyl curcumin analogues as potential anti-inflammatory agents
DOI:
https://doi.org/10.46542/pe.2023.232.200206Keywords:
Anti-inflammatory, Docking, In vivo, Pyrazolopyridine, SynthesisAbstract
Background: Pyrazolopyridines are heterocyclic compounds with nitrogen atoms in the ring, and they have been used as one of the important pharmacophores in drug design. Pyrazole derivatives have been synthesised and applied in the pharmaceutical industry as active drugs. The recent commercial success of pyrazole COX-2 inhibitors has brought even more attention to the significance of this heterocyclic ring in medicinal chemistry.
Objective: This study aimed to synthesise new compounds as anti-inflammatory candidates from the pyrazolopyridine group.
Method: Synthesis was carried out using the Claisen-Schmidt reaction through condensation of substituted benzaldehyde and 4-piperidone to produce mono-ketone curcumin analogues, which were then cyclised with phenylhydrazine. The results of the synthesis were characterised using FT-IR, 1H-NMR, and MS. Docking analysis was performed on the 3LN1 protein with MOE 2021.0901. Furthermore, an in vivo anti-inflammatory test was applied using a plethysmometer.
Results: The synthesis results obtained two pyrazolopyridine compounds, and the docking results showed that both of these synthesised compounds could interact with the COX-2 receptor binding site.
Conclusion: Compound 2 demonstrated good anti-inflammatory activities. This strategy is in the preliminary stages of identifying novel substances that may be used as anti-inflammatory agents in the future.
References
Angeli, A., Kartsev, V., Petrou, A., Lichitsky, B. Komogortsev, A., Pinteala, M., Geronikaki, A. & Supuran, C.T. (2022). Pyrazolo[4,3-c]Pyridine Sulfonamides as Carbonic Anhydrase inhibitors: Synthesis, Biological and In Silico Studies, Pharmaceuticals, 15(3):316. https://doi.org/10.3390/ph15030316
Bilavendran, J.D., Manikandan, A., Thangarasu, P. & Sivakumar, K. (2020), Synthesis and Discovery of pyrazolo-pyridine analogues as inflammation medication through pro-and inflammatory cytokine and COX-2 inhibition assessments. Bioorganic chemistry, 94:103484. https://doi.org/10.1016/j.bioorg.2019.103484
El Gohary, N.S., Gabr, M.T. & Shaaban, M.I. (2019). Synthesis Molecular modelling and biological evaluation of new Pyrazolo[3,4-b]pyridine analogues as potential antimicrobial, anti-quorum-sensing and anticancer agents, Bioorganic Chemistry, 89(2019):102976. https://doi.org/10.1016/j.bioorg.2019.102976
El-Sayed, R., Althagafi, I., Morad, M., El-Bahy, S.M. & El-Metwaly, N. (2021), synthesis and investigation of heterocyclic systems as pharmacological agents with conformational study and surface activity, Journal of Molecular Structure, 1240:130597. https://doi.org/10.1016/j.molstruc.2021.130597
Giannouli, V., Lougiakis, N., Kostakis, I.K., Pouli, N., Marakos, P., Skaltsounis, A.L., Horne, D.A., Nam, S., Gioti, K. & Tenta, R. (2020), Design and Synthesis of New Substituted Pyrazolopyridines with Potent Antiproliferative Activity, Medicinal Chemistry, 16(2):176–191. https://doi.org/10.2174/1573406415666190222130225
Gomez, A.A., Godoy, A. & Portilla, J. (2021), Functional Pyrazolo [1,5-a]pyrimidines: Current Approaches in Synthetic Transformations and Uses as an Antitumor Scaffold. Molecules, 26(9):2708. https://doi.org/10.3390/molecules26092708
Karrouchi, K., Radi, S., Ramli, Y., Taoufik, J., Mabkhot, Y.N., Al-aizari, F.A. & Ansar, M. (2018), A Review: Synthesis and Pharmacological Activity of Pyrazole Derivatives: A Review, Molecules, 23(1):134. https://doi.org/10.3390/molecules23010134
Mantzonidou, M., Pontiki, E. & Hadjipavlou-Litina, D. (2021), Pyrazole and Pyrazolines as Anti-Inflammatory Agents. Molecules, 26(11):3439. https://doi.org/10.3390/molecules26113439
Arulraj, R., Sivakumar, S., Suresh, S. & Anitha, K. (2020). Synthesis, vibrational spectra, DFT calculations, Hirshfeld surface analysis and molecular docking study of 3-chloro-3-methyl-2,6-diphenylpiperidin-4-one, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 232:(118166). https://doi.org/10.1016/j.saa.2020.118166
Rashad, A.E., Shamroukh, A.H., Abdel-Megeid, R.E. & Ali, H.S. (2014). Synthesis and Isomerisation of Some Novel Pyrazolopyrimidine and Pyrazolotriazolopyrimidine Derivatives, Molecules, 19(5):5459-5469. https://doi.org/10.3390/molecules19055459
Secrieru, A., O’Neill, P.M. & Cristiano, M.L.S. (2020). Revisiting the Structure and Chemistry of 3(5)-Substituted Pyrazole, Molecules, 25(1): 42. https://doi.org/10.3390/molecules25010042
Zhao, Z., Dai, X., Li, C., Wang, X., Tian, J., Feng, Y., Xie. J., Ma, C., Nie, Z., Fan, P., Qian, M., He, X., Wu, S., Zhang, Y. & Zheng, X. (2019), Pyrazolon structural motif in medicinal chemistry: Retrospect and prospect, European Journal of Medicinal Chemistry, 186:111893. https://doi.org/10.1016/j.ejmech.2019.111893