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Journals / Avrupa Yaşam Bilimleri Dergisi / 2026 / Volume: 1 Issue: 1

Design, synthesis and in-vitro COX inhibitory profiles of a new series of tetrazole-based hydrazones

Mehlika Dilek Altıntop(ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PROFESSIONAL PHARMACEUTICAL SCIENCES, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY)0000-0002-8159-663X
Belgin Sever(ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PROFESSIONAL PHARMACEUTICAL SCIENCES, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY)0000-0003-4847-9711
Halide Edip Temel(ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BASIC PHARMACEUTICAL SCIENCES, DEPARTMENT OF BIOCHEMISTRY)0000-0002-5233-1165
Zafer Asım Kaplancıklı(ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PROFESSIONAL PHARMACEUTICAL SCIENCES, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY)0000-0003-2252-0923
Ahmet Özdemir(ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PROFESSIONAL PHARMACEUTICAL SCIENCES, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY)0000-0003-0280-5550
Pages
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Publication Date
2022-04-29
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

In general, 1-methyl-1H-tetrazole moiety resulted in selective COX-1 inhibition, whereas 1-phenyl-1H-tetrazole moiety gave rise to preferential COX-2 inhibition.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Inhibition of cyclooxygenases (COXs), by selective and nonselective inhibitors, is a favorable approach for pharmacologic intervention in a variety of disorders such as cancer.
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Key Findings & Data:For this purpose, a new class of tetrazole-hydrazone hybrids (1-12) was designed.
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Conclusion & Impact:In general, 1-methyl-1H-tetrazole moiety resulted in selective COX-1 inhibition, whereas 1-phenyl-1H-tetrazole moiety gave rise to preferential COX-2 inhibition.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Cyclooxygenase · hydrazone · synthesis

Abstract

Inhibition of cyclooxygenases (COXs), by selective and nonselective inhibitors, is a favorable approach for pharmacologic intervention in a variety of disorders such as cancer. For this purpose, a new class of tetrazole-hydrazone hybrids (1-12) was designed. A facile and efficient procedure was applied for the preparation of compounds 1-12, which were tested for their inhibitory activities towards cyclooxygenases (COXs) by means of an in vitro colorimetric method. The most potent and selective COX-1 inhibitors were determined as 2-[(1-methyl-1H-tetrazol-5-yl)thio]-N'-(4-(piperidin-1-yl)benzylidene)acetohydrazide (1) (40.88±2.79%) and 2-[(1-methyl-1H-tetrazol-5-yl)thio]-N'-(4-(morpholin-4-yl)benzylidene)acetohydrazide (2) (39.80±2.78%), whereas the most potent and selective COX-2 inhibitor was found as 2-[(1-phenyl-1H-tetrazol-5-yl)thio]-N'-(4-(pyrrolidin-1-yl)benzylidene)acetohydrazide (10) (42.38±1.16%). In general, 1-methyl-1H-tetrazole moiety resulted in selective COX-1 inhibition, whereas 1-phenyl-1H-tetrazole moiety gave rise to preferential COX-2 inhibition.

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Cite This Article

Altıntop, M. D., Sever, B., Temel, H. E., Kaplancıklı, Z. A., Özdemir, A. (2022). Design, synthesis and in-vitro COX inhibitory profiles of a new series of tetrazole-based hydrazones. Avrupa Yaşam Bilimleri Dergisi, Volume: 1 Issue: 1. https://doi.org/10.55971/EJLS.1095818

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References (27)

  1. Rouzer CA, Marnett LJ. Structural and chemical biology of the interaction of cyclooxygenase with substrates and non-steroidal anti-inflammatory drugs. Chem Rev. (2020);120:7592-7641. https://dx.doi.org/10.1021/acs.chemrev.0c00215
  2. Brock TG, McNish RW, Peters-Golden M. Arachidonic acid is preferentially metabolized by cyclooxygenase-2 to prostacyclin and prostaglandin E2. J Biol Chem. (1999);274(17):11660-6. https://doi.org/10.1074/jbc.274.17.11660
  3. Mazaleuskaya, LL, Ricciotti E. Druggable prostanoid pathway. Adv Exp Med Biol. (2020);1274:29-54. https://doi.org/10.1007/978-3-030-50621-6_3
  4. Pannunzio A, Coluccia M. Cyclooxygenase-1 (COX-1) and COX-1 inhibitors in cancer: A review of oncology and medicinal chemistry literature. Pharmaceuticals (2018);11:101. https://doi.org/10.3390/ph11040101
  5. Sharma V, Bhatia P, Alam O, Javed Naim M, Nawaz F, Ahmad Sheikh A, Jha M. Recent advancement in the discovery and development of COX-2 inhibitors: Insight into biological activities and SAR studies (2008-2019). Bioorg Chem. (2019);89:103007. https://doi.org/10.1016/j.bioorg.2019.103007
  6. Zidar N, Odar K, Glavac D, Jerse M, Zupanc T, Stajer D. Cyclooxygenase in normal human tissues – is COX-1 really a constitutive isoform, and COX-2 an inducible isoform? J Cell Mol Med. (2009);13:3753-3763. https://doi.org/10.1111/j.1582-4934.2008.00430.x
  7. Yu T, Lao X, Zheng H. Influencing COX-2 activity by COX related pathways in inflammation and cancer. Mini Rev Med Chem. (2016);16:1230-1243. https://doi.org/10.2174/1389557516666160505115743
  8. Gandhi J, Khera L, Gaur N, Paul C, Kaul R. Role of modulator of inflammation cyclooxygenase-2 in gammaherpesvirus mediated tumorigenesis. Front Microbiol. (2017);8:538. https://doi.org/10.3389/fmicb.2017.00538
  9. Caiazzo E, Ialenti A, Cicala C. The relatively selective cyclooxygenase-2 inhibitor nimesulide: What's going on? Eur J Pharmacol. (2019);848:105-111. https://doi.org/10.1016/j.ejphar.2019.01.044
  10. Vitale P, Tacconelli S, Perrone MG, Malerba P, Simone L, Scilimati A, Lavecchia A, Dovizio M, Marcantoni E, Bruno A, Patrignani P. Synthesis, pharmacological characterization, and docking analysis of a novel family of diarylisoxazoles as highly selective cyclooxygenase-1 (COX-1) inhibitors. J Med Chem. (2013);56(11):4277-4299. https://doi.org/10.1021/jm301905a
  11. Perrone MG, Scilimati A, Simone L, Vitale P. Selective COX-1 inhibition: A therapeutic target to be reconsidered. Curr Med Chem. (2010);17(32):3769-805. https://doi.org/10.2174/092986710793205408
  12. Carullo G, Galligano F, Aiello F. Structure-activity relationships for the synthesis of selective cyclooxygenase 2 inhibitors: An overview (2009-2016). Medchemcomm. (2016);8(3):492-500. https://doi.org/10.1039/c6md00569a
  13. Kumar P, Narasimhan B. Hydrazides/hydrazones as antimicrobial and anticancer agents in the new millennium. Mini-Rev Med Chem. (2013);13:971-987. https://doi.org/10.2174/1389557511313070003
  14. Rollas S, Küçükgüzel SG. Biological activities of hydrazone derivatives. Molecules (2007);12(8):1910-1939. https://doi.org/10.3390/12081910
  15. Narang R, Narasimhan B, Sharma S. A review on biological activities and chemical synthesis of hydrazide derivatives. Curr Med Chem. 2012;19(4):569-612. https://10.2174/092986712798918789
  16. Mali SN, Thorat BR, Gupta DR, Pandey A. Mini-review of the importance of hydrazides and their derivatives—Synthesis and biological activity. Eng. Proc. (2021);11:21. https://doi.org/10.3390/ASEC2021-11157
  17. Ju Z, Su M, Hong J, La Kim E, Moon HR, Chung HY, Kim S, Jung JH. Design of balanced COX inhibitors based on anti-inflammatory and/or COX-2 inhibitory ascidian metabolites. Eur J Med Chem. (2019);180:86-98. https://doi.org/10.1016/j.ejmech.2019.07.016
  18. Abdelgawad MA, Labib MB, 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);74:212-220. http://dx.doi.org/10.1016/j.bioorg.2017.08.014
  19. Gorantla V, Gundla R, Jadav SS, Anugu SR, Chimakurthy J, Nidasanametla SK, Korupolu R. Molecular hybrid design, synthesis and biological evaluation of N-phenyl sulfonamide linked N-acyl hydrazone derivatives functioning as COX-2 inhibitors: new anti-inflammatory, anti-oxidant and anti-bacterial agents. New J Chem. (2017);41:13516-13532. https://doi.org/10.1039/c7nj03332j
  20. Mohammed KO, Nissan YM. Synthesis, molecular docking, and biological evaluation of some novel hydrazones and pyrazole derivatives as anti-inflammatory agents. Chem Biol Drug Des. (2014);84(4):473-488. https://doi.org/10.1111/cbdd.12336
  21. El-Sayed MA-A, Abdel-Aziz NI, Abdel-Aziz AA-M, El-Azab AS, Asiri YA, ElTahir KEH. Design, synthesis, and biological evaluation of substituted hydrazone and pyrazole derivatives as selective COX-2 inhibitors: Molecular docking study. Bioorg Med Chem. (2011);19:3416-3424. https://doi.org/10.1016/j.bmc.2011.04.027
  22. Xiong Q, Dong S, Chen Y, Liu X, Feng X. Asymmetric synthesis of tetrazole and dihydroisoquinoline derivatives by isocyanide-based multicomponent reactions. Nat Commun. (2019);10:2116. https://doi.org/10.1038/s41467-019-09904-5
  23. Lamie PF, Philoppes JN, Azouz AA, Safwat NM. Novel tetrazole and cyanamide derivatives as inhibitors of cyclooxygenase-2 enzyme: design, synthesis, anti-inflammatory evaluation, ulcerogenic liability and docking study. J Enzyme Inhib Med Chem. (2017);32:805-820. https://doi.org/10.1080/14756366.2017.1326110
  24. Labib MB, Fayez AM, El-Nahass ES, Awadallah M, Halim PA. Novel tetrazole-based selective COX-2 inhibitors: Design, synthesis, anti-inflammatory activity, evaluation of PGE2, TNF-α, IL-6 and histopathological study. Bioorg Chem. (2020);104:104308. https://doi.org/10.1016/j.bioorg.2020.104308
  25. Wei C-X, Bian M, Gong G-H. Tetrazolium compounds: synthesis and applications in medicine. Molecules (2015);20:5528-5553. https://doi.org/10.3390/molecules20045528
  26. Altıntop MD, Kaplancıklı ZA, Akalın Çiftçi G, Demirel R. Synthesis and biological evaluation of thiazoline derivatives as new antimicrobial and anticancer agents. Eur J Med Chem. (2014);74:264-277. https://doi.org/10.1016/j.ejmech.2013.12.060
  27. Altıntop MD, Özdemir A, Turan-Zitouni G, Ilgın S, Atlı Ö, İşcan G, Kaplancıklı ZA. Synthesis and biological evaluation of some hydrazone derivatives as new anticandidal and anticancer agents. Eur J Med Chem. (2012);58:299-307. https://doi.org/10.1016/j.ejmech.2012.10.011