Design and construction of novel pyridine-pyrimidine hybrids as selective COX-2 suppressors: anti-inflammatory potential, ulcerogenic profile, molecular modeling and ADME/Tox studies

References

• Abbas, S. E., Awadallah, F. M., Ibrahin, N. A., Said, E. G., & Kamel, G. M. (2012). New quinazolinone–pyrimidine hybrids: Synthesis, anti-inflammatory, and ulcerogenicity studies. European Journal of Medicinal Chemistry, 53, 141–149. https://doi.org/10.1016/j.ejmech.2012.03.050
   PubMed Web of Science ®Google Scholar
• Abdelgawad, M. A., Al-Sanea, M. M., Musa, A., Elmowafy, M., El-Damasy, A. K., Azouz, A. A., Ghoneim, M. M., & Bakr, R. B. (2022). Docking study, synthesis, and anti-inflammatory potential of some new pyridopyrimidine-derived compounds. Journal of Inflammation Research, 15, 451–463. https://doi.org/10.2147/JIR.S343263
   PubMedGoogle Scholar
• Abdelgawad, M. A., Bakr, R. B., & Azouz, A. A. (2018). Novel pyrimidine-pyridine hybrids: Synthesis, cyclooxygenase inhibition, anti-inflammatory activity and ulcerogenic liability. Bioorganic Chemistry, 77, 339–348. https://doi.org/10.1016/j.bioorg.2018.01.028
   PubMed Web of Science ®Google Scholar
• 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. https://doi.org/10.1016/j.bioorg.2017.07.007
   PubMed Web of Science ®Google Scholar
• Abdelgawad, M. A., Bakr, R. B., Ahmad, W., Al-Sanea, M. M., & Elshemy, H. A. (2019). New pyrimidine-benzoxazole/benzimidazole hybrids: Synthesis, antioxidant, cytotoxic activity, in vitro cyclooxygenase and phospholipase A2-V inhibition. Bioorganic Chemistry, 92, 103218. https://doi.org/10.1016/j.bioorg.2019.103218
   PubMed Web of Science ®Google Scholar
• 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(16), 1899–1912. https://doi.org/10.4155/fmc-2017-0115
   Web of Science ®Google Scholar
• Abdelgawad, M. A., Elkanzi, N. A., Musa, A., Ghoneim, M. M., Ahmad, W., Elmowafy, M., Abdelhaleem Ali, A. M., Abdelazeem, A. H., Bukhari, S. N., El-Sherbiny, M., Abourehab, M. A., & Bakr, R. B. (2022). Optimization of pyrazolo [1, 5-a] pyrimidine based compounds with pyridine scaffold: Synthesis, biological evaluation and molecular modeling study. Arabian Journal of Chemistry, 15(8), 104015. https://doi.org/10.1016/j.arabjc.2022.104015
   Web of Science ®Google Scholar
• Abdelgawad, M. A., Musa, A., Almalki, A. H., Alzarea, S. I., Mostafa, E. M., Hegazy, M. M., Mostafa-Hedeab, G., Ghoneim, M. M., Parambi, D. G. T., Bakr, R. B., Al-Muaikel, N. S., Alanazi, A. S., Alharbi, M., Ahmad, W., Bukhari, S. N. A., & Al-Sanea, M. M. (2021). Novel phenolic compounds as potential dual EGFR and COX-2 inhibitors: Design, semisynthesis, in vitro biological evaluation and in silico insights. Drug Design, Development and Therapy, 15, 2325–2337. https://doi.org/10.2147/DDDT.S310820
   PubMed Web of Science ®Google Scholar
• Abdellatif, K. R., & Bakr, R. B. (2018). New advances in synthesis and clinical aspects of pyrazolo [3, 4-d] pyrimidine scaffolds. Bioorganic Chemistry, 78, 341–357. https://doi.org/10.1016/j.bioorg.2018.03.032
   PubMed Web of Science ®Google Scholar
• Abdellatif, K. R., Abdelall, E. K., & Bakr, R. B. (2017). Nitric oxide-NASIDS donor prodrugs as hybrid safe anti-inflammatory agents. Current Topics in Medicinal Chemistry, 17(8), 941–955. https://doi.org/10.2174/1568026616666160927153435
   Web of Science ®Google Scholar
• Akhtar, W., Nainwal, L. M., Khan, M. F., Verma, G., Chashoo, G., Bakht, A., Iqbal, M., Akhtar, M., Shaquiquzzaman, M., & Alam, M. M. (2020). Synthesis, COX-2 inhibition and metabolic stability studies of 6-(4-fluorophenyl)-pyrimidine-5-carbonitrile derivatives as anticancer and anti-inflammatory agents. Journal of Fluorine Chemistry, 236, 109579. https://doi.org/10.1016/j.jfluchem.2020.109579
   Web of Science ®Google Scholar
• Almirante, L., Polo, L., Mugnaini, A., Provinciali, E., Rugarli, P., Biancotti, A., Gamba, A., & Murmann, W. (1965). Derivatives of imidazole. I. Synthesis and reactions of imidazo [1, 2-α] pyridines with analgesic, antiinflammatory, antipyretic, and anticonvulsant activity. Journal of Medicinal Chemistry, 8(3), 305–312. https://doi.org/10.1021/jm00327a007
   Web of Science ®Google Scholar
• Al-Sanea, M. M., Parambi, D. G. T., Shaker, M. E., Elsherif, H. A. M., Elshemy, H. A. H., Bakr, R. B., Al-Warhi, T. I. M., Gamal, M., & Abdelgawad, M. A. (2020). Design, synthesis, and in vitro cytotoxic activity of certain 2-[3-Phenyl-4-(pyrimidin-4-yl)-1 H-pyrazol1-yl] acetamide derivatives. Russian Journal of Organic Chemistry, 56(3), 514–520. https://doi.org/10.1134/S1070428020030239
   Web of Science ®Google Scholar
• Amr, A. E. G. E., Sayed, H. H., & Abdulla, M. M. (2005). Synthesis and reactions of some new substituted pyridine and pyrimidine derivatives as analgesic, anticonvulsant and antiparkinsonian agents. Archiv Der Pharmazie, 338(9), 433–440. https://doi.org/10.1002/ardp.200500982
   PubMed Web of Science ®Google Scholar
• Amr, A.-G. E., Mohamed, A. M., Mohamed, S. F., Abdel-Hafez, N. A., & Hammam, A. E.-F. G. (2006). Anticancer activities of some newly synthesized pyridine, pyrane, and pyrimidine derivatives. Bioorganic & Medicinal Chemistry, 14(16), 5481–5488. https://doi.org/10.1016/j.bmc.2006.04.045
   PubMed Web of Science ®Google Scholar
• Aouf, A., Bouaouina, S., Abdelgawad, M. A., Abourehab, M. A., & Farouk, A. (2022). In silico study for Algerian essential oils as antimicrobial agents against multidrug-resistant bacteria isolated from pus samples. Antibiotics, 11(10), 1317. https://doi.org/10.3390/antibiotics11101317
   Google Scholar
• Bakr, R. B., & Elkanzi, N. A. (2020). Preparation of some novel thiazolidinones, imidazolinones, and azetidinone bearing pyridine and pyrimidine moieties with antimicrobial activity. Journal of Heterocyclic Chemistry, 57(7), 2977–2989. https://doi.org/10.1002/jhet.4009
   Web of Science ®Google Scholar
• Bakr, R. B., Ghoneim, A. A., & Azouz, A. A. (2019). Selective cyclooxygenase inhibition and ulcerogenic liability of some newly prepared anti-inflammatory agents having thiazolo [4, 5-d] pyrimidine scaffold. Bioorganic Chemistry, 88, 102964. https://doi.org/10.1016/j.bioorg.2019.102964
   PubMed Web of Science ®Google Scholar
• Baraldi, P. G., Cacciari, B., Moro, S., Spalluto, G., Pastorin, G., Da Ros, T., Klotz, K.-N., Varani, K., Gessi, S., & Borea, P. A. (2002). Synthesis, biological activity, and molecular modeling investigation of new pyrazolo [4, 3-e]-1, 2, 4-triazolo [1, 5-c] pyrimidine derivatives as human A3 adenosine receptor antagonists. Journal of Medicinal Chemistry, 45(4), 770–780. https://doi.org/10.1021/jm0109614
   Web of Science ®Google Scholar
• Chebanov, V. A., Saraev, V. E., Gura, E. A., Desenko, S. M., & Musatov, V. I. (2005). Some aspects of reaction of 6-aminouracil and 6-amino-2-thiouracil with α, β-unsaturated ketones. Collection of Czechoslovak Chemical Communications, 70(3), 350–360. https://doi.org/10.1135/cccc20050350
   Google Scholar
• Cho, C. H., & Ogle, C. W. (1979). Cholinergic-mediated gastric mast cell degranulation with subsequent histamine H1-and H2-receptor activation in stress ulceration in rats. European Journal of Pharmacology, 55(1), 23–33. https://doi.org/10.1016/0014-2999(79)90144-4
   PubMed Web of Science ®Google Scholar
• Cryer, B., & Dubois, A. (1998). The advent of highly selective inhibitors of cyclooxygenase—A review. Prostaglandins & Other Lipid Mediators, 56(5–6), 341–361. https://doi.org/10.1016/s0090-6980(98)00064-1
   Web of Science ®Google Scholar
• Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7, 42717. https://doi.org/10.1038/srep42717
   Google Scholar
• de Freitas, R. F., & Schapira, M. (2017). A systematic analysis of atomic protein–ligand interactions in the PDB. MedChemComm, 8(10), 1970–1981. https://doi.org/10.1039/c7md00381a
   PubMed Web of Science ®Google Scholar
• De Sá, A.G.C., Long, Y., Portelli, S., Pires, D.E.V., & Ascher, D.B. (2022). toxCSM: comprehensive prediction of small molecule toxicity profiles. Briefings in Bioinformatics, 23(5). https://doi.org/10.1093/bib/bbac337
   Google Scholar
• Elkanzi, N. A., & Bakr, R. B. (2020). Microwave assisted, antimicrobial activity and molecular modeling of some synthesized newly pyrimidine derivatives using 1, 4-diazabicyclo [2.2. 2] octane as a catalyst. Letters in Drug Design & Discovery, 17(12), 1538–1551. https://doi.org/10.2174/1570180817999200802033351
   Google Scholar
• Elkanzi, N. A., Bakr, R. B., & Ghoneim, A. A. (2019). Design, synthesis, molecular modeling study, and antimicrobial activity of some novel pyrano [2, 3‐b] pyridine and pyrrolo [2, 3‐b] pyrano [2.3‐d] pyridine derivatives. Journal of Heterocyclic Chemistry, 56(2), 406–416. https://doi.org/10.1002/jhet.3412
   Web of Science ®Google Scholar
• Gomez, L., Massari, M. E., Vickers, T., Freestone, G., Vernier, W., Ly, K., Xu, R., McCarrick, M., Marrone, T., Metz, M., Yan, Y. G., Yoder, Z. W., Lemus, R., Broadbent, N. J., Barido, R., Warren, N., Schmelzer, K., Neul, D., Lee, D., … Breitenbucher, J. G. (2017). Design and synthesis of novel and selective phosphodiesterase 2 (PDE2a) inhibitors for the treatment of memory disorders. Journal of Medicinal Chemistry, 60(5), 2037–2051. https://doi.org/10.1021/acs.jmedchem.6b01793
   Web of Science ®Google Scholar
• Gras, M., Therrien, B., Süss-Fink, G., Casini, A., Edafe, F., & Dyson, P. J. (2010). Anticancer activity of new organo-ruthenium, rhodium and iridium complexes containing the 2-(pyridine-2-yl) thiazole N, N-chelating ligand. Journal of Organometallic Chemistry, 695(8), 1119–1125. https://doi.org/10.1016/j.jorganchem.2010.01.020
   Web of Science ®Google Scholar
• Helal, M. H., El-Awdan, S. A., Salem, M. A., Abd-Elaziz, T. A., Moahamed, Y. A., El-Sherif, A. A., & Mohamed, G. A. M. (2015). Synthesis, biological evaluation and molecular modeling of novel series of pyridine derivatives as anticancer, anti-inflammatory and analgesic agents. Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy, 135, 764–773. https://doi.org/10.1016/j.saa.2014.06.145
   PubMed Web of Science ®Google Scholar
• Hla, T., Bishop-Bailey, D., Liu, C., Schaefers, H., & Trifan, O. (1999). Cyclooxygenase-1 and-2 isoenzymes. International Journal of Biochemistry & Cell Biology, 31(5), 551–557. https://doi.org/10.1016/s1357-2725(98)00152-6
   PubMed Web of Science ®Google Scholar
• Kam, P., & See, A. U. L. (2000). Cyclo‐oxygenase isoenzymes: Physiological and pharmacological role. Anaesthesia, 55(5), 442–449. https://doi.org/10.1046/j.1365-2044.2000.01271.x
   Web of Science ®Google Scholar
• Kamat, V., Santosh, R., Poojary, B., Nayak, S. P., Kumar, B. K., Sankaranarayanan, M., Khanapure, S., Barretto, D. A., Vootla, S. K., & Faheem. (2020). Pyridine-and thiazole-based hydrazides with promising anti-inflammatory and antimicrobial activities along with their in silico studies. ACS Omega, 5(39), 25228–25239. https://doi.org/10.1021/acsomega.0c03386
   Web of Science ®Google Scholar
• Lacerda, R. B., de Lima, C. K. F., da Silva, L. L., Romeiro, N. C., Miranda, A. L. P., Barreiro, E. J., & Fraga, C. A. M. (2009). Discovery of novel analgesic and anti-inflammatory 3-arylamine-imidazo [1, 2-a] pyridine symbiotic prototypes. Bioorganic & Medicinal Chemistry, 17(1), 74–84. https://doi.org/10.1016/j.bmc.2008.11.018
   PubMed Web of Science ®Google Scholar
• Lee, H. W., Kim, B. Y., Ahn, J. B., Kang, S. K., Lee, J. H., Shin, J. S., Ahn, S. K., Lee, S. J., & Yoon, S. S. (2005). Molecular design, synthesis, and hypoglycemic and hypolipidemic activities of novel pyrimidine derivatives having thiazolidinedione. European Journal of Medicinal Chemistry, 40(9), 862–874. https://doi.org/10.1016/j.ejmech.2005.03.019
   PubMed Web of Science ®Google Scholar
• Liu, Y., Yang, X., Gan, J., Chen, S., Xiao, Z.-X., & Cao, Y. (2022). CB-Dock2: Improved protein–ligand blind docking by integrating cavity detection, docking and homologous template fitting. Nucleic Acids Research, 50(W1), W159–W164. https://doi.org/10.1093/nar/gkac394
   PubMed Web of Science ®Google Scholar
• Omar, M. A., Amr, A. E. G. E., & Al‐Salahi, R. A. (2010). Anti‐inflammatory, analgesic, anticonvulsant and antiparkinsonian activities of some pyridine derivatives using 2, 6‐disubstituted isonicotinic acid hydrazides. Archiv Der Pharmazie, 343(11–12), 648–656. https://doi.org/10.1002/ardp.201000088
   Web of Science ®Google Scholar
• Osiri, M., & Moreland, L. W. (1999). Specific cyclooxygenase 2 inhibitors: A new choice of nonsteroidal anti‐inflammatory drug therapy. Arthritis & Rheumatism, 12(5), 351–362. https://doi.org/10.1002/1529-0131(199910)12:5<351::AID-ART7>3.0.CO;2-L
   Google Scholar
• Putz, M. V., & Dudaş, N. A. (2013). Determining chemical reactivity driving biological activity from SMILES transformations: The bonding mechanism of anti-HIV pyrimidines. Molecules (Basel, Switzerland), 18(8), 9061–9116. https://doi.org/10.3390/molecules18089061
   Web of Science ®Google Scholar
• Quan, Z.-J., Liang, J.-L., Bai, L., Zhang, Z., Da, Y.-X., & Wang, X.-C. (2012). Focused microwave-assisted efficient and convenient synthesis of new pyrido [2, 3-d] pyrimidinone derivatives. Heterocyclic Communications, 18(5–6), 257–261. https://doi.org/10.1515/hc-2012-0131
   Web of Science ®Google Scholar
• Rowley, A. F., Knight, J., Lloyd-Evans, P., Holland, J. W., & Vickers, P. J. (1995). Eicosanoids and their role in immune modulation in fish—A brief overview. Fish & Shellfish Immunology, 5(8), 549–567. https://doi.org/10.1016/S1050-4648(95)80041-7
   Web of Science ®Google Scholar
• Siddiqi, Z. A., Khalid, M., Kumar, S., Shahid, M., & Noor, S. (2010). Antimicrobial and SOD activities of novel transition metal complexes of pyridine-2, 6-dicarboxylic acid containing 4-picoline as auxiliary ligand. European Journal of Medicinal Chemistry, 45(1), 264–269. https://doi.org/10.1016/j.ejmech.2009.10.005
   PubMed Web of Science ®Google Scholar
• Smith, W. L., DeWitt, D. L., & Garavito, R. M. (2000). Cyclooxygenases: Structural, cellular, and molecular biology. Annual Review of Biochemistry, 69(1), 145–182. https://doi.org/10.1146/annurev.biochem.69.1.145
   PubMedGoogle Scholar
• Sondhi, S. M., Jain, S., Dinodia, M., Shukla, R., & Raghubir, R. (2007). One pot synthesis of pyrimidine and bispyrimidine derivatives and their evaluation for anti-inflammatory and analgesic activities. Bioorganic & Medicinal Chemistry, 15(10), 3334–3344. https://doi.org/10.1016/j.bmc.2007.03.028
   PubMed Web of Science ®Google Scholar
• Sondhi, S. M., Singh, N., Johar, M., & Kumar, A. (2005). Synthesis, anti-inflammatory and analgesic activities evaluation of some mono, bi and tricyclic pyrimidine derivatives. Bioorganic & Medicinal Chemistry, 13(22), 6158–6166. https://doi.org/10.1016/j.bmc.2005.06.063
   PubMed Web of Science ®Google Scholar
• St-Onge, M., Flamand, N., Biarc, J., Picard, S., Bouchard, L., Dussault, A.-A., Laflamme, C., James, M. J., Caughey, G. E., Cleland, L. G., Borgeat, P., & Pouliot, M. (2007). Characterization of prostaglandin E2 generation through the cyclooxygenase (COX)-2 pathway in human neutrophils. Biochimica et Biophysica Acta, 1771(9), 1235–1245. https://doi.org/10.1016/j.bbalip.2007.06.002
   PubMed Web of Science ®Google Scholar
• Williams, D., Singh, M., & Hind, C. (2006). The effect of the withdrawal of rofecoxib on prescribing patterns of COX‐2 inhibitors in Scotland. British Journal of Clinical Pharmacology, 62(3), 366–368. https://doi.org/10.1111/j.1365-2125.2006.02691.x
   Web of Science ®Google Scholar
• Winter, C. A., Risley, E. A., & Nuss, G. W. (1962). Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.), 111(3), 544–547. https://doi.org/10.3181/00379727-111-27849
   PubMed Web of Science ®Google Scholar
• Zhuang, J., & Ma, S. (2020). Recent development of pyrimidine‐containing antimicrobial agents. ChemMedChem, 15(20), 1875–1886. https://doi.org/10.1002/cmdc.202000378
   Web of Science ®Google Scholar