Pyrazole as an anti-inflammatory scaffold
A comprehensive review
Keywords:
inflammation, heterocyclic compounds, pyrazole, docking studies, binding affinityAbstract
Inflammation is a common component behind pathophysiology of many chronic diseases like cardiovascular, arthritis, bowel disorders, cancer, chronic wounds, and lesions which are the most significant cause of death in the world, according to the World Health Organization. Chronic inflammation associated diseases are expected to increase persistently by the next 30 years as 3 of 5 people die daily due to chronic inflammatory diseases. So, the prerequisite of novel anti-inflammatory agents has been noteworthy increased than ever. Heterocyclic compounds are being developed at the large pace over the most recent couple of decades due to their intriguing pharmacological activities. The most remarkable and well-known heterocyclic nucleus is pyrazole which has pulled the consideration of numerous specialists to explore its wide potential. Pyrazole derivatives are considered as valuable class of compounds owing to their extremely noticeable anti-inflammatory activity. This review delivers a vast summary of pyrazole derivatives developed last decade for their action against inflammation along with docking studies with a hope that it will be useful for medicinal chemists working in anti-inflammatory drug development.
Downloads
References
Chen L., Deng H., Cui H., Fang J., Zuo Z., Deng J.: Inflammatory responses and inflammation-associated diseases in organs, Oncotarget, 2018, 9(6), 7204. A
Pahwa R., Goyal A., Jialal I.: Chronic Inflammation. In: StatPearls; Treasure Island (FL): StatPearls Publishing; 2022, 300–14.
Ashour H.M.A., El-Ashmawy I.M., Bayad A.E.: Synthesis and pharmacological evaluation of new pyrazolyl benzenesulfonamides linked to polysubstituted pyrazoles and thiazolidinones as anti-inflammatory and analgesic agents. Monatshefte fur Chemie. 2016, 147(3), 605–18.
Abdelgawad M.A., Labib M.B., Abdel-Latif M.: Pyrazole-hydrazone derivatives as anti-inflammatory agents: Design, synthesis, biological evaluation, COX-1,2/5-LOX inhibition and docking study. Bioorg Chem. 2017, 74, 212–20.
Eftekhari-Sis B., Zirak M., Akbari A.: Arylglyoxals in synthesis of heterocyclic compounds. Chem Rev. 2013, 113(5), 2958–3043.
Kaur P, Chawla A. 1,2,4-triazole: A review of pharmacological activities. Int. Res. J. Pharm. 2017, 8(7), 10–29.
Faisal M., Saeed A., Hussain S., Dar P., Larik F.A.: Recent developments in synthetic chemistry and biological activities of pyrazole derivatives. J. Chem. Sci. 2019, 131, 70.
Ansari A., Ali A., Asif M., Shamsuzzaman.: Review: biologically active pyrazole derivatives. New. J. Chem. 2016, 41(1), 16-41.
Alam M.J., Alam O., Alam P., Naim M.J.: A Review on pyrazole chemical entity and Biological Activity. International Journal of Pharma Sciences and Research. 2015, 12(6), 1433-1442.
Poudyal B., Bharghav G.: A review of pyrazole an its derivative. Natl. J. Pharm. Sci. 2021, 1(1), 34-41.
Faria J.V., Vegi P.F., Miguita A.G.C., dos Santos M.S., Boechat N., Bernardino A.M.R.: Recently reported biological activities of pyrazole compounds. Bioorg. Med. Chem. 2017, 25(21), 5891–903.
Jadhav S., Peerzade N., Gawali R., Bhosale R., Kulkarni A., Varpe B.: Green synthesis and biological screening of some fluorinated pyrazole chalcones in search of potent anti-inflammatory and analgesic agents. Egypt. Pharm. J. 2020, 19(2), 172.
Abdellatif K.R.A, Abdelall E.K.A., Lamie P.F., Labib M.B., El-Nahaas E.S., Abdelhakeem M.M.: New pyrazole derivatives possessing amino/methanesulphonyl pharmacophore with good gastric safety profile: Design, synthesis, cyclooxygenase inhibition, anti-inflammatory activity and histopathological studies. Bioorg. Chem. 2020, 95, 103540.
Gedawy E.M., Kassab A.E., El Kerdawy A.M. Design, synthesis and biological evaluation of novel pyrazole sulfonamide derivatives as dual COX-2/5-LOX inhibitors. Eur. J. Med. Chem. 2020, 189, 112066.
Abdellatif K.R.A., Fadaly W.A.A., Kamel G.M., Elshaier Y.A.M.M., El-Magd M.A.: Design, synthesis, modeling studies and biological evaluation of thiazolidine derivatives containing pyrazole core as potential anti-diabetic PPAR-γ agonists and anti-inflammatory COX-2 selective inhibitors. Bioorganic Chemistry. 2019, 82, 86–99.
Abdellatif K.R.A., El-Saadi M.T., Elzayat S.G., Amin N.H.: New substituted pyrazole derivatives targeting COXs as potential safe anti-inflammatory agents. Future Med Chem. 2019, 11(16), 1871–87.
Abdellatif K.R.A., Fadaly W.A.A., Mostafa Y.A., Zaher D.M., Omar H.A.: Thiohydantoin derivatives incorporating a pyrazole core: Design, synthesis and biological evaluation as dual inhibitors of topoisomerase-I and cycloxygenase-2 with anti-cancer and anti-inflammatory activities. Bioorg Chem. 2019, 91, 103132.
Bharathi R., Santhi N.: Benzonitrile as a novel anti-Inflammatory scaffold : Synthesis , biological evaluation and docking studies. 2019, 126, 148–62.
Dennis Bilavendran J., Manikandan A., Thangarasu P., Sivakumar K.: Synthesis and discovery of pyrazolo-pyridine analogs as inflammation medications through pro- and anti-inflammatory cytokine and COX-2 inhibition assessments. Bioorg. Chem. 2020, 94, 103484.
El-Shoukrofy M.S, Abd El Razik H.A., AboulWafa O.M., Bayad A.E., El-Ashmawy I.M.: Pyrazoles containing thiophene, thienopyrimidine and thienotriazolopyrimidine as COX-2 selective inhibitors: Design, synthesis, in vivo anti-inflammatory activity, docking and in silico chemo-informatic studies. Bioorg. Chem. 2019, 85, 541–57.
Hassan G.S., Abdel Rahman D.E., Abdelmajeed E.A., Refaey R.H., Alaraby Salem M., Nissan Y.M. New pyrazole derivatives: Synthesis, anti-inflammatory activity, cycloxygenase inhibition assay and evaluation of mPGES. Eur J Med Chem. 2019, 171, 332–42.
Macarini A.F., Sobrinho T.U.C., Rizzi G.W., Correa R.: Pyrazole–chalcone derivatives as selective COX-2 inhibitors: Design, virtual screening, and in vitro analysis. Med Chem Res. 2019, 28(8), 1235–45.
Song M., Liu B., Yu S., He S., Liang Y., Li S.: New hydrazone derivatives of pyrazole-4-carboxaldehydes exhibited anti-inflammatory properties. Lett Drug Des Discov. 2019, 17(4), 502–11.
Taher A.T., Mostafa Sarg M.T., El-Sayed Ali N.R., Hilmy Elnagdi N.: Design, synthesis, modeling studies and biological screening of novel pyrazole derivatives as potential analgesic and anti-inflammatory agents. Bioorg Chem. 2019, 89, 103023.
Tageldin G.N., Ibrahim T.M., Fahmy S.M., Ashour H.M., Khalil M.A., Nassra R.A.: Synthesis, modeling and biological evaluation of some pyrazolo[3,4-d]pyrimidinones and pyrazolo[4,3-e][1,2,4]triazolo[4,3-a]pyrimidinones as anti-inflammatory agents. Bioorg Chem. 2019, 90, 102844.
Zabiulla, Gulnaz A.R., Mohammed Y.H.E., Khanum S.A.: Design, synthesis and molecular docking of benzophenone conjugated with oxadiazole sulphur bridge pyrazole pharmacophores as anti inflammatory and analgesic agents. Bioorg Chem. 2019, 92, 103220.
Abdelgawad M.A., Labib M.B., Ali W.A.M., Kamel G., Azouz A.A., EL-Nahass E.S.: Design, synthesis, analgesic, anti-inflammatory activity of novel pyrazolones possessing aminosulfonyl pharmacophore as inhibitors of COX-2/5-LOX enzymes: Histopathological and docking studies. Bioorg Chem. 2018, 78, 103–14.
Abdellatif K.R.A., Fadaly W.A.A., Elshaier Y.A.M.M., Ali W.A.M., Kamel G.M.: Non-acidic 1,3,4-trisubstituted-pyrazole derivatives as lonazolac analogs with promising COX-2 selectivity, anti-inflammatory activity and gastric safety profile. Bioorg Chem. 2018, 77, 568–78.
Kulkarni R.C., Madar J.M., Shastri S.L., Shaikh F., Naik N.S., Chougale R.B.: Green synthesis of coumarin-pyrazolone hybrids: In vitro anticancer and anti-inflammatory activities and their computational study on COX-2 enzyme. Chem Data Collect. 2018, 17–18, 497–506.
Abd El Razik H.A., Badr M.H., Atta A.H., Mouneir S.M., Abu-Serie M.M.: Benzodioxole–pyrazole hybrids as anti-inflammatory and analgesic agents with COX-1,2/5-LOX inhibition and antioxidant potential. Arch Pharm (Weinheim). 2017, 350(5), 1–19.
Lokeshwari D.M., Achutha D.K., Srinivasan B., Shivalingegowda N., Krishnappagowda L.N., Kariyappa A.K. Synthesis of novel 2-pyrazoline analogues with potent anti-inflammatory effect mediated by inhibition of phospholipase A2: Crystallographic, in silico docking and QSAR analysis. Bioorganic Med Chem Lett. 2017, 27(16), 3806–11.
Nossier E.S., Fahmy H.H., Khalifa N.M., El-Eraky W.I., Baset M.A., McPhee D.J.: Design and synthesis of novel pyrazole-substituted different nitrogenous heterocyclic ring systems as potential anti-inflammatory agents. Molecules. 2017, 22(4), 1–16.
Abdellatif K.R.A., Fadaly W.A.A.: Design, synthesis, cyclooxygenase inhibition and biological evaluation of new 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives possessing amino/methanesulfonyl pharmacophore. Bioorganic Chemistry. 2017, 70, 57–66.
Abdel-Sayed M.A., Bayomi S.M., El-Sherbeny M.A., Abdel-Aziz N.I., Eltahir K.E.H., Shehatou G.S.G.: Synthesis, anti-inflammatory, analgesic, COX-1/2 inhibition activities and molecular docking study of pyrazoline derivatives. Bioorganic Med Chem. 2016, 24(9), 2032–42.
Alam M.J., Alam O., Khan S.A., Naim M.J., Islamuddin M., Deora G.S.: Docking Studies of Hybrid Pyrazole Analogues. Dove Press J. 2016, 10, 3529–43.
El-Feky S.A.H., Abd El-Samii Z.K., Osman N.A., Lashine J., Kamel M.A., Thabet H.K.: Synthesis, molecular docking and anti-inflammatory screening of novel quinoline incorporated pyrazole derivatives using the Pfitzinger reaction II. Bioorg Chem. 2015, 58, 104–16.
Kamble R.D., Meshram R.J., Hese S.V., More R.A., Kamble S.S., Gacche R.N.: Synthesis and in silico investigation of thiazoles bearing pyrazoles derivatives as anti-inflammatory agents. Comput Biol Chem. 2016, 61, 86–96.
Somakala K., Amir M., Sharma V., Wakode S.: Synthesis and pharmacological evaluation of pyrazole derivatives containing sulfonamide moiety. Monatshefte fur Chemie. 2016, 147(11), 2017–29.
Bansal S., Bala M., Suthar S.K., Choudhary S., Bhattacharya S., Bhardwaj V.: Design and synthesis of novel 2-phenyl-5-(1,3-diphenyl-1H-pyrazol-4-yl)-1, 3,4-oxadiazoles as selective COX-2 inhibitors with potent anti-inflammatory activity. Eur J Med Chem 2014, 80, 167–74.
El-Moghazy S.M., Barsoum F.F., Abdel-Rahman H.M., Marzouk A.A. Synthesis and anti-inflammatory activity of some pyrazole derivatives. Med Chem Res. 2012, 21(8), 1722–33.
Published
How to Cite
Issue
Section
Copyright (c) 2022 International journal of health sciences

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Articles published in the International Journal of Health Sciences (IJHS) are available under Creative Commons Attribution Non-Commercial No Derivatives Licence (CC BY-NC-ND 4.0). Authors retain copyright in their work and grant IJHS right of first publication under CC BY-NC-ND 4.0. Users have the right to read, download, copy, distribute, print, search, or link to the full texts of articles in this journal, and to use them for any other lawful purpose.
Articles published in IJHS can be copied, communicated and shared in their published form for non-commercial purposes provided full attribution is given to the author and the journal. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
This copyright notice applies to articles published in IJHS volumes 4 onwards. Please read about the copyright notices for previous volumes under Journal History.