Drug Dev Res. 2021 Apr;82(2):167-197. doi: 10.1002/ddr.21753. Epub 2020 Nov 02.
"Azole" as privileged heterocycle for targeting the inducible cyclooxygenase enzyme.
Drug development research
Parteek Prasher, Mousmee Sharma
Affiliations
Affiliations
- UGC Sponsored Centre for Advanced Studies, Department of Chemistry, Guru Nanak Dev University, Amritsar, India.
- Department of Chemistry, University of Petroleum & Energy Studies, Energy Acres, Dehradun, India.
- Department of Chemistry, Uttaranchal University, Arcadia Grant, Dehradun, India.
PMID: 33137216
DOI: 10.1002/ddr.21753
Abstract
An over-expression of COX-2 isoenzyme belonging to the Cyclooxygenase Enzyme Family triggers the overproduction of pro-inflammatory prostaglandins that instigate the development of chronic inflammation and related disorders. Hence, the rationally designed drugs for mitigating over-activity of COX-2 isoenzyme play a regulatory role toward the alleviation of the progression of these disorders. However, a selective COX-2 inhibition chemotherapy prompts several side effects that necessitate the identification of novel molecular scaffolds for deliberating state-of-the-art drug designing strategies. The heterocyclic "azole" scaffold, being polar and hydrophilic, possesses remarkable physicochemical advantages for designing physiologically active molecules capable of interacting with a wide range of biological components, including enzymes, peptides, and metabolites. The substituted derivatives of azole nuclei enable a comprehensive SAR analysis for the appraisal of bioactive profile of the deliberated molecules for obtaining the rationally designed compounds with prominent activities. The comprehensive SAR analysis readily prompted the identification of Y-shaped molecules and the eminence of bulkier group for COX-2 selective inhibition. This review presents an epigrammatic collation of the pharmacophore-profile of the chemotherapeutics based on azole motif for a selective targeting of the COX-2 isoenzyme.
© 2020 Wiley Periodicals LLC.
Keywords: arachidonic acid; azoles; inflammation
References
- Abdelgawad, M. A., Bakr, R. B., EL-Gendy, A. O., Kamel, G. M., Azouz, A. A., & Bukhari, S. N. A. (2017). Discovery of a COX-2 selective inhibitor hit with anti-inflammatory activity and gastric ulcer protective effect. Future Medicinal Chemistry, 9, 1899-1912. - PubMed
- Abdelgawad, M. A., Bakr, R. B., & Omar, H. A. (2017). Design, synthesis and biological evaluation of some novel benzothiazole/benzoxazole and/or benzimidazole derivatives incorporating a pyrazole scaffold as antiproliferative agents. Bioorganic Chemistry, 74, 82-90. - PubMed
- Abdellatif, K. R. A., Abdelgawad, M. A., Elshemy, H. A. H., & Alsayed, S. S. R. (2016). Design, synthesis and biological screening of new 4-thiazolidinone derivatives with promising COX-2 selectivity, anti-inflammatory activity and gastric safety profile. Bioorganic Chemistry, 64, 1-12. - PubMed
- Abdellatif, K. R. A., & Fadaly, W. A. A. (2017). New 1,2-diaryl-4-substituted-benzylidene-5-4H-imidazolone derivatives: Design, synthesis and biological evaluation as potential anti-inflammatory and analgesic agents. Bioorganic Chemistry, 72, 123-129. - PubMed
- Abdellatif, K. R. A., Fadaly, W. A. A., Elshaier, Y. A. M. M., Ali, W. A. M., & Kamel, G. M. (2018). Non-acidic 1,3,4-trisubstituted-pyrazole derivatives as lonazolac analogs with promising COX-2 selectivity, anti-inflammatory activity and gastric safety profile. Bioorganic Chemistry, 77, 568-578. - PubMed
- Abdellatif, K. R. A., Fadaly, W. A. A., Kamel, G. M., Elshaier, Y. A. M. M., & El-Magd, M. A. (2019). 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, 82, 86-99. - PubMed
- Agalave, S. G., Maujan, S. R., & Pore, V. S. (2011). Click chemistry: 1,2,3-triazoles as pharmacophores. Chemistry: An Asian Journal, 6, 2696-2718. - PubMed
- Alegaon, S. G., Hirpara, M. B., Alagawadi, K. R., Hullatti, K. K., & Kashniyal, K. (2014). Synthesis of novel pyrazole-thiadiazole hybrid as potential potent and selective cyclooxygenase-2 (COX-2) inhibitors. Bioorganic & Medicinal Chemistry Letters, 24, 5324-5329. - PubMed
- Al-Hourani, B. J., Al-Awaida, W., Matalka, K. Z., El-Barghouti, M. I., Alsoubani, F., & Wuest, F. (2016). Structure-activity relationship of novel series of 1,5-disubstituted tetrazoles as cyclooxygenase-2 inhibitors: Design, synthesis, bioassay screening and molecular docking studies. Bioorganic & Medicinal Chemistry Letters, 26, 4757-4762. - PubMed
- Al-Hourani, B. J., El-Barghouti, M. I., Al-Awaida, W., Mc Donald, R., Fattash, I. A., El Soubani, F., & Wuest, F. (2020). Biomolecular docking, synthesis, crystal structure, and bioassay studies of 1-[4-(2-chloroethoxy)phenyl]-5-[4-(methylsulfonyl)phenyl]-1H-tetrazole and 2-(4-(5-(4-(methylsulfonyl)phenyl)-1H-tetrazol-1-yl)phenoxy)ethyl nitrate. Journal of Molecular Structure, 1202, 127323. - PubMed
- Al-Hourani, B. J., El-Barghouti, M. I., Mc Donald, R., Al-Awaida, W., Sharma, S. K., & Wuest, F. (2016). Synthesis and crystal structure of N-[(dimethylamino)methylidene]-4-[1-(4-nitrophenyl)-1H-tetrazol-5-yl]-benzenesulfonamide: Molecular docking and bioassay studies as cyclooxygenase-2 inhibitor. Journal of Molecular Structure, 1119, 220-226. - PubMed
- Al-Hourani, B. J., Sharma, S. K., Kaur, J., & Wuest, F. (2015). Synthesis, bioassay studies, and molecular docking of novel 5-substituted 1H tetrazoles as cyclooxygenase-2 (COX-2) inhibitors. Medicinal Chemistry Research, 24, 78-85. - PubMed
- Al-Hourani, B. J., Sharma, S. K., Mane, J. Y., Tuszynski, J., Baracos, V., Kniess, T., Suresh, M., Pietzsch, J., & Wuest, F. (2011). Synthesis and evaluation of 1,5-diaryl-substituted tetrazoles as novel selective cyclooxygenase-2 (COX-2) inhibitors. Bioorganic & Medicinal Chemistry Letters, 21, 1823-1826. - PubMed
- Al-Hourani, B. J., Sharma, S. K., Suresh, M., & Wuest, F. (2012). Novel 5-substituted 1H-tetrazoles as cyclooxygenase-2 (COX-2) inhibitors. Bioorganic & Medicinal Chemistry Letters, 22, 2235-2238. - PubMed
- Almansa, C., Alfon, J., Arriba, A. F., Cavalcanti, F. L., Escamilla, I., Gomez, L. A., Miralles, A., Soliva, R., Bartroli, J., Carceller, E., Merlos, M., & Rafanell, J. C. (2003). Synthesis and structure-activity relationship of a new series of COX-2 selective inhibitors: 1,5-Diarylimidazoles. Journal of Medicinal Chemistry, 46, 3463-3475. - PubMed
- Amin, N. H., Mohammed, A. A., & Abdellatif, K. R. A. (2018). Novel 4-methylsulfonylphenyl derivatives as NSAIDS with preferential COX-2 inhibition. Future Medicinal Chemistry, 10, 53-70. - PubMed
- Angajala, K., Vianala, S., Macha, R., Raghavender, M., Thupurani, M. K., & Pathi, P. J. (2016). Synthesis, anti-inflammatory, bactericidal activities and docking studies of novel 1,2,3-triazoles derived from ibuprofen using click chemistry. Springerplus, 5, 423. - PubMed
- Assadieskandar, A., Amirhamzeh, A., Salehi, M., Ozadali, K., & Ostad, S. N. (2013). Synthesis, cyclooxygenase inhibitory effects, and molecular modeling study of 4-aryl-5-(4-(methylsulfonyl)phenyl)-2-alkylthio and −2-alkylsulfonyl-1H-imidazole derivatives. Bioorganic & Medicinal Chemistry, 21, 2355-2362. - PubMed
- Bakhle, Y. S. (2001). COX-2 and cancer: A new approach to an old problem. British Journal of Pharmacology, 134, 1137-1150. - PubMed
- Bakhle, Y. S., & Bottling, R. M. (1996). Cyclooxygenase-2 and its regulation in inflammation. Mediators of Inflammation, 5, 305-323. - PubMed
- Barghash, R. F., Geronikaki, A., & Abdou, W. M. (2018). Synthesis of a series of substituted Thiazole derivatives: New COX-2 enzyme inhibitors for colon cancer and inflammation treatment. ChemistrySelect, 3, 13329-13337. - PubMed
- Belal, A., & Abdelgawad, M. A. (2017). New benzothiazole/benzoxazole-pyrazole hybrids with potential as COX inhibitors: Design, synthesis and anticancer activity evaluation. Research on Chemical Intermediates, 43, 3859-3872. - PubMed
- Bhardwaj, A., Kaur, J., Wuest, M., & Wuest, F. (2017). In situ click chemistry generation of cyclooxygenase-2 inhibitors. Nature Communications, 8, 1. - PubMed
- Bice, J. S., Jones, B. R., Chamberlain, G. R., & Baxter, G. F. (2016). Nitric oxide treatments as adjuncts to reperfusion in acute myocardial infarction: A systematic review of experimental and clinical studies. Basic Research in Cardiology, 111, 23. - PubMed
- Bonandi, E., Christodoulou, M. S., Fumagalli, G., Perdicchia, D., Rastelli, G., & Passarella, D. (2017). The 1,2,3-triazole ring as bioisostere in medicinal chemistry. Drug Discovery Today, 22, 1572-1581. - PubMed
- Britt, R. D., Locy, M. L., Tipple, T. E., Nelin, L. D., & Rogers, L. K. (2012). Lipopolysaccharide induced cyclooxygenase-2 expression in mouse transformed clara cells. Cellular Physiology and Biochemistry, 29, 213-222. - PubMed
- Cai, H., Huang, X., Xu, S., Shen, H., Zhang, P., Huang, Y., Jiang, J., Sun, Y., Jiang, B., Wu, X., Yao, H., & Xu, J. (2016). Discovery of novel hybrids of diaryl-1,2,4-triazoles and caffeic acid as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase for cancer therapy. European Journal of Medicinal Chemistry, 108, 89-103. - PubMed
- Cannon, C. P., & Cannon, P. J. (2012). COX-2 inhibitors and cardiovascular risk. Science, 336, 1386-1387. - PubMed
- Carullo, G., Galligano, F., & Aiello, F. (2017). Structure-activity relationships for the synthesis of selective cyclooxygenase-2 inhibitors. An overview (2009-2016). Medicinal Chemistry Communications, 8, 492-500. - PubMed
- Chawla, P., Kalra, S., Kumar, R., Singh, R., & Saraf, S. K. (2019). Novel 2-(substituted phenyl Imino)-5-benzylidene-4-thiazolidinonesas possible non-ulcerogenic tri-action drug candidates: Synthesis, characterization, biological evaluation and docking studies. Medicinal Chemistry Research, 28, 340-359. - PubMed
- Cipollone, F., & Fazia, M. L. (2006). COX-2 and atherosclerosis. Journal of Cardiovascular Pharmacology, 47, S26-S36. - PubMed
- Dannenberg, A. J., Lippman, S. M., Mann, J. R., Subbaramaiah, K., & DuBois, R. N. (2005). Cyclooxygenase2- and epidermal growth factor receptor: Pharmacologic targets for chemoprevention. Journal of Clinical Oncology, 23, 254-266. - PubMed
- Dheer, D., Singh, V., & Shankar, R. (2017). Medicinal attributes of 1,2,3-triazoles: Current developments. Bioorganic Chemistry, 71, 30-54. - PubMed
- El-Achkar, G. A., Jouni, M., Mrad, M. F., Hirz, T., Hachem, N. E., Khalaf, A., Hammoud, S., Kazan, H. F., Eid, A. A., Badran, B., Merhi, R. A., Hachem, A., Hamade, E., & Habib, A. (2015). Thiazole derivatives as inhibitors of cyclooxygenases in vitro and in vivo. European Journal of Pharmacology, 750, 66-73. - PubMed
- Eleftheriou, P., Geronikaki, A., Litina, D. H., Vicini, P., Filz, O., Filimonov, D., Poroikov, V., Chaudhery, S. S., Roy, K. K., & Saxena, A. K. (2012). Fragment-based design, docking, synthesis, biological evaluation and structure-activity relationships of 2-benzo/benzisothiazolimino-5-aryliden-4-thiazolidinones as cycloxygenase/lipoxygenase inhibitors. European Journal of Medicinal Chemistry, 47, 111-124. - PubMed
- Elie, J., Vercouillie, J., Arlicot, N., Lemaire, L., Bidault, R., Bodard, S., Hosselet, C., Deloye, J.-B., Chalon, S., Emond, P., Guilloteau, D., Buron, F., & Routier, S. (2019). Design of selective COX-2 inhibitors in the (aza)indazole series. Chemistry, in vitro studies, radiochemistry and evaluations in rats of a [18F] PET tracer. Journal of Enzyme Inhibition and Medicinal Chemistry, 34, 1-7. - PubMed
- Elsayed, M. S. A., Chang, S., & Cushman, M. (2018). Ligand-free, palladacycle-facilitated Suzuki coupling of hindered 2-arylbenzothiazole derivatives yields potent and selective COX-2 inhibitors. Organic & Biomolecular Chemistry, 16, 108-118. - PubMed
- Elzahhar, P. A., El Wahab, S. M. A., Elagawany, M., Daabees, H., Bilal, A. S. F., El-Yazbi, A. F., Eid, A. H., Alaaeddine, R., Hegazy, R. R., Allam, R. M., Helmy, M. W., Elgendy, B., Angeli, A., El-Hawash, S. A., & Supuran, C. T. (2020). Expanding the anticancer potential of 1,2,3-triazoles via simultaneously targeting Cyclooxygenase-2, 15-lipoxygenase and tumor-associated carbonic anhydrases. European Journal of Medicinal Chemistry, 200, Article, 112439. - PubMed
- Fadaly, W. A. A., Elshaier, Y. A. M. M., Hassanein, E. H. M., & Abdellatif, K. R. A. (2020). New 1,2,4-triazole/pyrazole hybrids linked to oxime moiety as nitric oxide donor celecoxib analogs: Synthesis, cyclooxygenase inhibition anti-inflammatory, ulcerogenicity, anti-proliferative activities, apoptosis, molecular modeling and nitric oxide release studies. Bioorganic Chemistry, 98, 103752. https://doi.org/10.1016/j.bioorg.2020.103752. - PubMed
- Fiorucci, S., Santucci, L., & Distrutti, E. (2007). NSAIDs, coxibs, CINOD and H2S-releasing NSAIDs: What lies beyond the horizon. Digestive and Liver Disease, 39, 1043-1051. - PubMed
- Fitzgerald, G. A. (2004). Coxibs and cardiovascular disease. The New England Journal of Medicine, 351, 1709-1711. - PubMed
- Fitzpatrick, F. A. (2004). Cyclooxygenase enzymes: Regulation and function. Current Pharmaceutical Design, 10, 577-588. - PubMed
- Geronikaki, A. A., Lagunin, A. A., Litina, D. I. H., Eleftheriou, P. T., Filimonov, D. A., Poroikov, V. V., Alam, I., & Saxena, A. K. (2008). Computer-aided discovery of anti-inflammatory Thiazolidinones with dual cyclooxygenase/Lipoxygenase inhibition. Journal of Medicinal Chemistry, 51, 1601-1609. - PubMed
- Geusens, P. (2009). Naproxcinod, a new cyclooxygenase-inhibiting nitric oxide donator (CINOD). Expert Opinion on Biological Therapy, 9, 649-657. - PubMed
- Gierse, J. K., McDonald, J. J., Hauser, S. D., Rangwala, S. H., Koboldt, C. M., & Seibert, K. (1996). A single amino acid difference between cyclooxygenase-1 and 2reverses the selectivity of COX-2 specific inhibitors. The Journal of Biological Chemistry, 271, 15810-15814. - PubMed
- Goodsell, D. S. (2000). The molecular perspective: Cyclooxygenase-2. The Oncologist, 5, 169-171. - PubMed
- Goradel, N. H., Najafi, M., Salehi, E., Farhood, B., & Mortezaee, K. (2019). Cyclooxygenase in cancer: A review. Journal of Cellular Physiology, 234, 5683-5699. - PubMed
- Gorantla, V., Gundla, R., Jadav, S. S., Anugu, S. R., Chimakurthy, J., Rao, K., & Korupolu, R. (2017). New anti-inflammatory hybrid N- acyl Hydrazone-linked Isoxazole derivatives as COX-2 inhibitors:Rational design, synthesis and biological evaluation. ChemistrySelect, 2, 8091-8100. - PubMed
- Granstrom, E. (1984). The arachidonic acid cascade. Inflammation, 8, S15-S25. - PubMed
- Gudis, K., & Sakamoto, C. (2005). The role of cyclooxygenase in gastric mucosal protection. Digestive Diseases and Sciences, 50, S16-S23. - PubMed
- Guslandi, M. (2007). Gastrointestinal safety of NSAIDs versus COX-2 inhibitor. The Lancet, 369, P1344-P1345. - PubMed
- Haider, S., Alam, M. S., Hamid, H., Shafi, S., Dhulap, A., Hussain, F., Alam, P., Umar, S., Pasha, M. A. Q., Bano, S., Nazreen, S., Ali, Y., & Kharbanda, C. (2014). Synthesis of novel 1,2,3-triazole based benzoxazolinones: Their TNF-α based molecular docking with in-vivo anti-inflammatory, antinociceptive activities and ulcerogenic risk evaluation. European Journal of Medicinal Chemistry, 81, 204-217. - PubMed
- Hawkey, C. J., & Skelly, M. M. (2002). Gastrointestinal safety of selective COX-2 inhibitors. Current Pharmaceutical Design, 8, 1077-1089. - PubMed
- He, L.-Y., Zhang, S.-S., Peng, D.-X., Guan, L.-P., & Wang, S.-H. (2020). Synthesis and evaluations of selective Cox-2 inhibitory effects: Benzo[D]Thiazol analogs. Bioorganic & Medicinal Chemistry Letters, 30, 127376. - PubMed
- Hla, T., Bishop-Bailey, D., Liu, C. H., Schaefers, H. J., & Trifan, O. C. (1999). Cyclooxygenase-1 and 2-isoenzymes. The International Journal of Biochemistry & Cell Biology, 31, 551-557. - PubMed
- Hoogstraate, J., Andersson, L. I., Berge, O.-G., Jonzon, B., & Ojteg, G. (2003). COX-2 inhibiting nitric oxide donors (CINODs): A new paradigm in the treatment of pain and inflammation. Inflammopharmacology, 11, 423-428. - PubMed
- Huff, R. G., Bayram, E., Tan, H., Knutson, S. T., Knaggs, M. H., Richon, A. B., Santago, P., & Fetrow, J. S. (2005). Chemical and structural diversity in cyclooxygenase protein active sites. Chemistry & Biodiversity, 2, 1533-1552. - PubMed
- Jacob, J., & Manju, S. L. (2020). Identification and development of thiazole leads as COX-2/5-LOX inhibitors through in-vitro and in-vivo biological evaluation for anti-inflammatory activity. Bioorganic Chemistry, 100, 103882. - PubMed
- Jiang, B., Huang, X., Yao, H., Jiang, J., Wu, X., Jiang, S., Wang, Q., Lu, T., & Xu, J. (2014). Discovery of potential anti-inflammatory drugs: Diaryl-1,2,4-triazoles bearing N-hydroxyurea moiety as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase. Organic & Biomolecular Chemistry, 12, 2114-2127. - PubMed
- Jiang, B., Zeng, Y., Li, M.-J., Xu, J.-Y., Zhang, Y.-N., Wang, Q.-J., Sun, N.-Y., Lu, T., & Wu, X.-M. (2010). Design, synthesis, and biological evaluation of 1,5-Diaryl-1,2,4-triazole derivatives as selective Cyclooxygenase-2 inhibitors. Archiv der Pharmazie-Chemistry in Life Sciences, 343, 500-508. - PubMed
- Kage, K., Fujita, N., Oh-Hara, T., Ogata, E., Fujita, T., & Tsuruo, T. (1999). Basic fibroblast growth factor induces cyclooxygenase-2 expression in endothelial cells derived from bone. Biochemical and Biophysical Research Communications, 254(254), 259-263. - PubMed
- Kamble, R. D., Meshram, R. J., Hese, S. V., More, R. A., Kamble, S. S., Gacche, R. N., & Dawane, B. S. (2016). Synthesis and in silico investigation of thiazoles bearing pyrazoles derivatives as anti-inflammatory agents. Computational Biology and Chemistry, 61, 86-96. - PubMed
- Kaur, A., Pathak, D. P., Sharma, V., & Wakode, S. (2018a). Synthesis, biological evaluation and docking study of a new series of di-substituted benzoxazole derivatives as selective COX-2 inhibitors and anti-inflammatory agents. Bioorganic & Medicinal Chemistry, 26, 891-902. - PubMed
- Kaur, A., Pathak, D. P., Sharma, V., & Wakode, S. (2018b). Synthesis, molecular docking, and pharmacological evaluation of N-(2-(3,5-dimethoxyphenyl)benzoxazole-5-yl)benzamide derivatives as selective COX-2 inhibitors and anti-inflammatory agents. Archiv der Pharmazie-Chemistry in Life Sciences, 351, 1800008. - PubMed
- Khan, A., Diwan, A., Thabet, H. K., Imran, M., & Bakht, M. A. (2020). Discovery of novel Pyridazine-based Cyclooxygenase-2 inhibitors with a promising gastric safety profile. Molecules, 25, 2002. - PubMed
- Khanna, I. K., Weier, R. M., Yu, Y., Xu, X. D., Koszyk, F. J., Collins, P. W., Koboldt, C. M., Veenhuizen, A. W., Perkins, W. E., Casler, J. J., Masferrer, J. L., Zhang, Y. Y., Gregory, S. A., Seibert, K., & Isakson, P. C. (1997). 1,2-Diarylimidazoles as potent, cyclooxygenase-2 selective, and orally active antiinflammatory agents. Journal of Medicinal Chemistry, 40, 1634-1647. - PubMed
- Kharb, R., & Sharma, P. C. (2011). Yar, M.S. pharmacological significance of triazole scaffold. Journal of Enzyme Inhibition and Medicinal Chemistry, 26, 1-21. - PubMed
- Kodela, R., Chattopadhyay, M., Martinez-Velasquez, C. A., & Kashifi, K. (2015). NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications. Biochemical Pharmacology, 98, 564-572. - PubMed
- Kumari, P., Mishra, V. S., Narayana, C., Khanna, A., Chakrabarty, A., & Sagar, R. (2020). Design and efficient synthesis of pyrazoline and isoxazole bridged indole C-glycoside hybrids as potential anticancer agents. Scientific Reports, 10, 6660. - PubMed
- Lamie, P. F., Philoppes, J. N., Azouz, A. A., & Safwat, N. M. (2017). Novel tetrazole and cyanamide derivatives as inhibitors of cyclooxygenase-2 enzyme: Design, synthesis, anti-inflammatory evaluation, ulcerogenic liability and docking study. Journal of Enzyme Inhibition and Medicinal Chemistry, 32, 805-820. - PubMed
- Leslie, C. C. (2004). Regulation of the specific release of arachidonic acid by cytosolic phospholipase A2. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 70, 373-376. - PubMed
- Linton, M. R. F., & Fazio, S. (2008). Cyclooxygenase products and atherosclerosis. Drug Discovery Today Therapeutic Strategies, 5, 25-36. - PubMed
- Liu, W., Reinmuth, N., Stoeltzing, O., Parikh, A. A., Tellez, C., Williams, S., Jung, Y. D., Fan, F., Takeda, A., Akagi, M., Bar-Eli, M., Gallick, G. E., & Ellis, L. M. (2003). Cyclooxygenase-2 is upregulated by interleukin-1β in human colorectal cancer cells via multiple signaling pathways. Cancer Research, 63, 3632-3636. - PubMed
- Lucido, M. J., Orlando, B. J., Vecchio, A. J., & Malkowski, M. G. (2016). Crystal structure of aspirin-acetylated human cyclooxygenase-2; insights into the formation of products with reversed stereochemistry. Biochemistry, 55, 1226-1238. - PubMed
- Maghraby, M. T. E., Ghadir, O. M. F. A., Moty, S. G. A., Ali, A. Y., & Salem, O. I. A. (2020). Novel class of benzimidazole-thiazole hybrids: The privileged scaffolds of potent anti-inflammatory activity with dual inhibition of cyclooxygenase and 15-lipoxygenase enzymes. Bioorganic & Medicinal Chemistry, 28, 115403. - PubMed
- Malkowski M.G. (2017) Encyclopedia of Inorganic and Bioinoorganic Chemistry, https://doi.org/10.1002/9781119951438.eibc0547.pub2. - PubMed
- Mamidyala, S. K., & Finn, M. G. (2010). In situ click chemistry: Probing the binding landscapes of biological molecules. Chemical Society Reviews, 39, 1252-1261. - PubMed
- Mancini, J. A., Riendeau, D., Falgueyret, J.-P., Vickers, P. J., & O'Neill, G. P. (1995). Arginine 120 of prostaglandin G/H synthase-1 is required for the inhibition by nonsteroidal anti-inflammatory drugs containing a carboxylic acid moiety. The Journal of Biological Chemistry, 270, 29372-29377. - PubMed
- Mantry, P., Shah, A., & Sundaram, U. (2003). Celecoxib associated esophagitis: Review of gastrointestinal side effects from cox-2 inhibitors. Journal of Clinical Gastroenterology, 37, 61-63. - PubMed
- Marnett, L. J. (2000). Cyclooxygenase mechanisms. Current Opinion in Chemical Biology, 4, 545-552. - PubMed
- Matthys, K. E., & Bult, H. (1997). Nitric oxide functions in atherosclerosis. Mediators of Inflammation, 6, 3-21. - PubMed
- May, G. R., Crook, P., Moore, P. K., & Page, C. P. (1991). The role of nitric oxide as an endogenous regulator of platelet and neutrophil activation within the pulmonary circulation of the rabbit. British Journal of Pharmacology, 102, 759-763. - PubMed
- Mboyne, U. R., Wada, M., Rieke, C. J., Tang, H. Y., Dewitt, D. L., & Smith, D. L. (2006). The 19 amino acid cassette of cyclooxygenase-2 mediates entry of the protein into the ER-associated degradation system. The Journal of Biological Chemistry, 281, 35770-35778. - PubMed
- Medeiros, R., Figueiredo, C. P., Pandolfo, P., Duarte, F. S., Prediger, R. D., Passos, G. F., & Calixto, J. B. (2010). The role of TNF-alpha signaling pathway on COX-2 upregulation and cognitive decline induced by beta-amyloid peptide. Behavioural Brain Research, 209, 165-173. - PubMed
- Melnikova, I. (2005). Future of COX-2 inhibitors. Nature Reviews. Drug Discovery, 4, 453-454. - PubMed
- Movahed, M. A., Daraei, B., Shahosseini, S., Esfahanizadeh, M., & Zarghi, A. (2019). Design, synthesis, and biological evaluation of new pyrazino[1,2-a ]benzimidazole derivatives as selective cyclooxygenase (COX-2) inhibitors. Archiv der Pharmazie-Chemistry in Life Sciences, 352, 1800265. - PubMed
- Murahari, M., Mahajan, V., Neeladri, S., Kumar, M. S., & Mayur, Y. C. (2019). Ligand based design and synthesis of pyrazole based derivatives as selective COX-2 inhibitors. Bioorganic Chemistry, 86, 583-597. - PubMed
- Muscara, M. N., & Wallace, J. L. (2006). COX-2 inhibiting nitric oxide donors (CINODs): Potential benefits on cardiovascular and renal function. Cardiovascular & Hematological Agents in Medicinal Chemistry, 4, 155-164. - PubMed
- Naaz, F., Pallavi, M. C. P., Shafi, S., Mulakayala, N., Yar, M. S., & Kumar, H. M. S. (2018). 1,2,3-triazole tethered Indole-3-glyoxamide derivatives as multiple inhibitors of 5-LOX, COX-2 & tubulin: Their anti-proliferative & anti-inflammatory activity. Bioorganic Chemistry, 81, 1-20. - PubMed
- Navidpour, L., Amini, M., Shafaroodi, H., Abdi, K., Ghahremani, M. H., Dehpour, A. R., & Shafiee, A. (2006). Design and synthesis of new water-soluble tetrazolide derivatives of celecoxib and rofecoxib as selective cyclooxygenase-2 (COX-2) inhibitors. Bioorganic & Medicinal Chemistry Letters, 16, 4483-4487. - PubMed
- Navidpour, L., Shadnia, H., Shafaroodi, H., Amini, M., Dehpour, A. R., & Shafiee, A. (2007). Design, synthesis, and biological evaluation of substituted 2-alkylthio-1,5-diarylimidazoles as selective COX-2 inhibitors. Bioorganic & Medicinal Chemistry, 15, 1976-1982. - PubMed
- Navidpour, L., Shafaroodi, H., Abdi, K., Amini, M., Ghahremani, M. H., Dehpour, A. R., & Shafiee, A. (2006). Design, synthesis, and biological evaluation of substituted 3-alkylthio-4,5-diaryl-4H-1,2,4-triazoles as selective COX-2 inhibitors. Bioorganic & Medicinal Chemistry, 14, 2507-2517. - PubMed
- Neha, Dwivedi, A. R., Kumar, R., & Kumar, V. (2018). Recent synthetic strategies for monocyclic azole nucleus and its role in drug discovery and development. Current Organic Synthesis, 15, 321-340. - PubMed
- Neochoritis, C. G., Zhao, T., & Domling, A. (2019). Tetrazoles by multicomponent reactions. Chemical Reviews, 119, 1970-2042. - PubMed
- Omar, Y. M., Abdu-Allah, H. H. M., & Moty, S. G. A. (2018). Synthesis, biological evaluation and docking study of 1,3,4-thiadiazole-thiazolidinone hybrids as anti-inflammatory agents with dual inhibition of COX-2 and 15-LOX. Bioorganic Chemistry, 80, 461-471. - PubMed
- Omar, Y. M., Moty, S. G. A., & Abdul-Allah, H. H. M. (2020). Further insight into the dual COX-2 and 15-LOX anti-inflammatory activity of 1,3,4-thiadiazole-thiazolidinone hybrids: The contribution of the substituents at 5th positions is size dependent. Bioorganic Chemistry, 97, 103657. - PubMed
- Paul-Clark, M., ELsheikh, W., Kirkby, N., Chan, M., Devchand, P., Agbor, T. A., Flannigan, K. L., Cheadle, C., Freydin, M., Lanaro, A., Mitchell, J. A., & Wallace, J. L. (2016). Profound chemopreventive effects of a hydrogen sulfide-releasing NSAID in APCMin/+ mouse model of intestinal tumorigenesis. PLoS One, 11, e0147289. - PubMed
- Perrone, M. G., Vitale, P., Panella, A., Ferorelli, S., Contino, M., Lavecchia, A., & Scilimati, A. (2016). Isoxazole-based-scaffold inhibitors targeting cyclooxygenases (COXs). ChemMedChem, 11, 1172-1187. - PubMed
- Prasher, P., Mudila, H., Sharma, M., & Khati, B. (2019). Developmental perspectives of the drugs targeting enzyme-instigated inflammation: A mini review. Medicinal Chemistry Research, 28, 417-449. - PubMed
- Prasher, P., Pooja, V., & Singh, P. (2014). Lead modification: Amino acid appended indoles as highly effective 5-LOX inhibitors. Bioorganic & Medicinal Chemistry, 22, 1642-1648. - PubMed
- Prasher, P., & Sharma, M. (2018). Medicinal chemistry of acridines and its analogues. MedChemComm, 9, 1589-1618. - PubMed
- Prasher, P., & Sharma, M. (2019). Tailored therapeutics based on 1,2,3-1H-triazoles: A mini review. Medicinal Chemistry Communications, 10, 1302-1328. - PubMed
- Prasher, P., Sharma, M., Aljabali, A. A., Gupta, G., Negi, P., Kapoor, D. N., Singh, I., Zacconi, F., Pinto, T. J. A., Silva, M. W., Bakshi, H., Chellappan, D. K., Tambuwala, M. M., & Dua, K. (2020). Hybrid molecules based on 1,3,5-triazine as potential therapeutics: A focused review. Drug Development Research. https://doi.org/10.1002/ddr.21704. - PubMed
- Prasher, P., Sharma, M., Zacconi, F., Gupta, G., Aljabali, A. A., Mishra, V., Tambuwala, M. M., Kapoor, D. N., Negi, P., Pinto, T. J. A., Singh, I., Chellappan, D. K., & Dua, K. (2020). Synthesis and anticancer properties of azole based chemotherapeutics as emerging chemical moieties: A comprehensive review. Current Organic Chemistry, 24. https://doi.org/10.2174/1385272824999200820152501. - PubMed
- Ragab, F. A., Heiba, H. I., El-Gazzar, M. G., Abou-Seri, S. M., El-Sabbagh, W. A., & El-Hazek, R. M. (2016). Synthesis of novel thiadiazole derivatives as selective COX-2 inhibitors. MedChemComm, 7, 2309-2327. - PubMed
- Raghavendra, N. M., Jyothsna, A., Rao, A. V., & Subrahmanyam, C. V. S. (2012). Synthesis, pharmacological evaluation and docking studies of N-(benzo[d]thiazol-2-yl)-2-(piperazin-1-yl)acetamide analogs as COX-2 inhibitors. Bioorganic & Medicinal Chemistry Letters, 22, 820-823. - PubMed
- Rahman, H. M. A., & Ozadali, K. (2012). Trimethyl-4-oxo-4,5,6,7-tetrahydroindazole-1-acetic acid: A new Lead compound with selective COX-2 inhibitory activity. Archiv der Pharmazie-Chemistry in Life Sciences, 345, 878-883. - PubMed
- Ranatunge, R. R., Augustyniak, M., Bandarage, U. K., Earl, R. A., Ellis, J. L., Garvey, D. S., Janero, D. R., Letts, L. G., Martino, A. M., Murthy, M. G., et al. (2004). Synthesis and selective Cyclooxygenase-2 inhibitory activity of a series of novel, nitric oxide donor-containing Pyrazoles. Journal of Medicinal Chemistry, 47, 2180-2193. - PubMed
- Rathore, A., Rahman, M. U., Siddiqui, A. A., Ali, A., & Shaharyar, A. (2015). Synthesis and evaluation of benzimidazole derivatives as selective COX-2 inhibitors. Medicinal Chemistry, 11, 188-199. - PubMed
- Rathore, A., Rahman, M. U., Siddiqui, A. A., Ali, A., & Shaharyar, M. (2014). Design and synthesis of Benzimidazole analogs endowed with oxadiazole as selective COX-2 inhibitor. Archiv der Pharmazie-Chemistry in Life Sciences, 347, 923-935. - PubMed
- Rawat, C., Kukal, S., Dahiya, U. R., & Kukreti, R. (2019). Cyclooxygenase-2 (COX-2) inhibitors: Future therapeutic strategies for epilepsy management. Journal of Neuroinflammation, 16, 197. - PubMed
- Ricciotti, E., & Fitzgerald, G. A. (2011). Prostaglandins and inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology, 31, 986-1000. - PubMed
- Ricciotti, E., Yu, Y., Grosser, T., & Fitzgerald, G. A. (2013). COX-2, the dominant source of prostacyclin. Proceedings of the National Academy of Sciences of the United States of America, 110, E183. - PubMed
- Rosati, O., Curini, M., Marcotullio, M. C., Macchiarulo, A., Perfumi, M., Mattioli, L., Rismondo, F., & Cravotto, G. (2007). Synthesis, docking studies and anti-inflammatory activity of 4,5,6,7-tetrahydro-2H-indazole derivatives. Bioorganic & Medicinal Chemistry, 15, 3463-3473. - PubMed
- Rouzer, C. A., & Marnett, L. J. (2009). Cyclooxygenases: Structural and functional insights. Journal of Lipid Research, 50, S29-S34. - PubMed
- Saeed, E., & Alireza, F. (2006). Synthesis of 4-(4-Methylsulfonylphenyl)-3-phenyl-2(3H )-thiazole Thione derivatives as new potential COX-2 inhibitors. Chinese Journal of Chemistry, 24, 791-794. - PubMed
- Safaeian, L., Hajhashemi, V., & Ajoodanian, M. (2018). The effect of celecoxib on blood pressure and plasma oxidant/ antioxidant status in co-administration with glucocorticoid in rat. Biomedicine & Pharmacotherapy, 108, 1804-1808. - PubMed
- Sakya, S. M., Hou, X., Minich, M. L., Rast, B., Shavnya, A., DeMello, K. M. L., Cheng, H., Li, J., Jaynes, B. H., Mann, D. W., Petras, C. F., Siebel, S. B., & Haven, M. L. (2007). 5-heteroatom substituted pyrazoles as canine COX-2 inhibitors. Part III: Molecular modeling studies on binding contribution of 1-(5-methylsulfonyl)pyrid-2-yl and 4-nitrile. Bioorganic & Medicinal Chemistry Letters, 17, 1067-1072. - PubMed
- Sarnpitak, P., Mujumdar, P., Morisseau, C., Hwang, S. H., Hammock, B., Lurchenko, V., Zozulya, S., Gavalas, A., Geronikaki, A., Ivanenkov, Y., & Krasavin, M. (2014). Potent, orally available, selective COX-2 inhibitors based on 2-imidazoline core. European Journal of Medicinal Chemistry, 84, 160-172. - PubMed
- Schneider, C., Boeglin, W. E., & Brash, A. R. (2004). Identification of two cyclooxygenase active sire residues, leucine 384 and glycine 526, that control carbon ring cyclization in prostaglandin biosynthesis. The Journal of Biological Chemistry, 279, 4404-4414. - PubMed
- Shafi, S., Alam, M. M., Mulakayala, N., Mulakayala, C., Vanaja, G., Kalle, A. M., Pallu, R., & Alam, M. S. (2012). Synthesis of novel 2-mercapto benzothiazole and 1,2,3-triazole based bis-heterocycles: Their anti-inflammatory and anti-nociceptive activities. European Journal of Medicinal Chemistry, 49, 324-333. - PubMed
- Sharpless, K. B., & Manetsch, R. (2006). In situ click chemistry: A powerful means for lead discovery. Expert Opinion on Drug Discovery, 1, 525-538. - PubMed
- Shen, F.-Q., Wang, Z.-C., Wu, S.-Y., Ren, S.-Z., Man, R.-J., Wang, B.-Z., & Zhu, H.-L. (2017). Synthesis of novel hybrids of pyrazole and coumarin as dual inhibitors of COX-2 and 5-LOX. Bioorganic & Medicinal Chemistry Letters, 27, 3653-3660. - PubMed
- Signoroni, S., Frattini, M., Negri, T., Pastore, E., Tamborini, E., Casieri, P., Orsenigo, M., Da Riva, L., Radice, P., Sala, P., Gronchi, A., Bertario, L., Pierotti, M. A., & Pilotti, S. (2007). Cyclooxygenase-2 and platelet-derived growth factor receptors as potential targets in treating aggressive Fibromatosis. Clinical Cancer Research, 13, 5034-5040. - PubMed
- Singh, P., Prasher, P., Dhillon, P., & Bhatti, R. (2015). Indole based peptidomimetics as anti-inflammatory and anti-hyperalgesic agents: Dual inhibition of 5-LOX and COX-2 enzymes. European Journal of Medicinal Chemistry, 97, 104-123. - PubMed
- Stitham, J., Midgett, C., Martin, K. A., & Hwa, J. (2011). Prostacyclin: An inflammatory paradox. Frontiers in Pharmacology, 2, 24. - PubMed
- Sun, S. X., Lee, K. Y., Bertram, C. T., & Goldstein, J. L. (2007). Withdrawal of COX-2 selective inhibitors rofecoxib and valdecoxib: Impact on NSAID and gastroprotective drug prescribing and utilization. Current Medical Research and Opinion, 23, 1859-1866. - PubMed
- Swetha, K. S., Parameshwar, R., Reddy, B. M., & Babu, V. H. (2013). Synthesis of novel pyrazolyl tetrazoles as selective COX-2 inhibitors. Medicinal Chemistry Research, 22, 4886-4892. - PubMed
- Tageldin, G. N., Fahmy, S. M., Ashour, H. M., Khalil, M. A., Nassra, R. A., & Labouta, I. M. (2018). Design, synthesis and evaluation of some pyrazolo[3,4-d]pyrimidine derivatives bearing thiazolidinone moiety as anti-inflammatory agents. Bioorganic Chemistry, 80, 164-173. - PubMed
- Tariq, S., Alam, O., & Amir, M. (2018). Synthesis, p38α MAP kinase inhibition, anti-inflammatory activity, and molecular docking studies of 1,2,4-triazole-based benzothiazole-2-amines. Archiv der Pharmazie-Chemistry in Life Sciences, 351, 1700304. - PubMed
- Taylor, R. D., MacCoss, M., & Lawson, A. D. G. (2014). Rings in drugs. Journal of Medicinal Chemistry, 57, 5845-5859. - PubMed
- Tepperman, B. L., & Whittle, B. J. R. (1992). Endogenous nitric oxide and sensory neuropeptides interact in the modulation of rat gastric microcirculation. British Journal of Pharmacology, 105, 171-175. - PubMed
- Thore, S. N., Gupta, S. V., & Baheti, K. G. (2013). Docking, synthesis, and pharmacological investigation of novel substituted thiazole derivatives as non-carboxylic, anti-inflammatory, and analgesic agents. Medicinal Chemistry Research, 22, 3802-3811. - PubMed
- Tiwari, A. K., Singh, V. P., Yadav, P., Gupta, G., Singh, A., Goel, R. K., Shinde, P., & Mohan, C. G. (2014). Synthesis, biological evaluation and molecular modeling study of pyrazole derivatives as selective COX-2 inhibitors and anti-inflammatory agents. Bioorganic Chemistry, 56, 8-15. - PubMed
- Vane, J. R., & Warner, T. D. (2000). Nomenclature for COX-2 inhibitors. The Lancet, 356, P1373-P1374. - PubMed
- Vecchio, A. J., Orlando, B. J., Nandagiri, R., & Malkowski, M. G. (2012). Investigating substrate promiscuity in cyclooxygenase-2. The role of Arg-120 and resides lining the hydrophobic groove. The Journal of Biological Chemistry, 287, 24619-24630. - PubMed
- Whittle, B. J. R. (2000). COX-1 and COX-2 products in the gut: Therapeutic impact of COX-2 inhibitors. Gut, 47, 320-325. - PubMed
- Williams, C. S., Mann, M., & DuBois, R. N. (1999). The role of cyclooxygenases in inflammation, cancer, and development. Oncogene, 18, 7908-7916. - PubMed
- Wuest, F., Tang, X., Kniess, T., Pietzsch, J., & Suresh, M. (2009). Synthesis and cyclooxygenase inhibition of various (aryl-1,2,3-triazole-1-yl)-methanesulfonylphenyl derivatives. Bioorganic & Medicinal Chemistry, 17, 1146-1151. - PubMed
- Yatam, S., Gundla, R., Jadav, S. S., Pedavenkatagari, N. R., Chimakurthy, J., Rani, N., & Kedam, T. (2018). Focused library design and synthesis of 2-mercapto benzothiazole linked 1,2,4-oxadiazoles as COX-2/5-LOX inhibitors. Journal of Molecular Structure, 1159, 193-204. - PubMed
- Yatam, S., Jadav, S. S., Gundla, K. P., Paidikondala, K., Ankireddy, A. R., Babu, B. N., Ahsan, M. J., & Gundla, R. (2019). 2-Mercapto Benzthiazole coupled benzyl Triazoles as new COX-2 inhibitors: Design, synthesis, biological testing and molecular modeling studies. ChemistrySelect, 4, 11081-11092. - PubMed
- Yatam, S., Jadav, S. S., Gundla, R., Gundla, K. P., Reddy, G. M., Ahsan, M. J., & Chimakurthy, J. (2018). Design, synthesis and biological evaluation of 2 (([5-aryl-1,2,4-oxadiazol-3-yl]methyl)thio)benzo[d]oxazoles: New Antiinflammatory and antioxidant agents. ChemistrySelect, 3, 10305-10310. - PubMed
- Yetik-Anacak, G., Sevin, G., Ozzayim, O., Dereli, M. V., & Ahmed, A. (2016). Hydrogen sulfide: A novel mechanism for the vascular protection by resveratrol under oxidative stress in mouse aorta. Vascular Pharmacology, 87, 76-82. - PubMed
- Zarghi, A., & Arfaei, S. (2011). Selective COX-2 inhibitors: A review of their structure-activity relationships. Iranian Journal of Pharmaceutical Research, 10, 65-683. - PubMed
- Zarghi, A., Reihanfard, H., Arfaei, S., Daraei, B., & Hedayati, M. (2012). Design and synthesis of new 1,2-diaryl-4,5,6,7-tetrahydro-1Hbenzo[d] imidazoles as selective cyclooxygenase (COX-2) inhibitors. Medicinal Chemistry Research, 21, 1869-1875. - PubMed
- Zarraga, I. G. E., & Schwarz, E. R. (2007). Coxibs and heart disease: What we have learned and what else we need to know. Journal of the American College of Cardiology, 49, 1-14. - PubMed
Publication Types