Synthesis, Biological Validation, and Docking Studies of Novel Purine Derivatives Containing Pyridopyrimidine, Pyrazolopyridine, and Pyranonapthyridine Rings^†

References

• L. A. Zhmurenko, G. M. Molodavkin, T. A. Voronina, and V. P. Lezina, “Synthesis and Antidepressant and Anxiolytic Activity of Derivatives of Pyrazolo[4,3-c]Pyridine and 4-Phenyl Hydrazinonicotinic Acids,” Pharmaceutical Chemistry Journal 46, no. 1 (2012): 15–9.
   Web of Science ®Google Scholar
• L. A. Smyth, T. P. Matthews, P. N. Horton, M. B. Hursthouse, and I. Collins, “Synthesis and Reactivity of 3-Amino-1H-Pyrazolo[4,3-c]Pyridin-4(5H)-Ones: Development of a Novel Kinase-Focussed Library,” Tetrahedron 66, no. 15 (2010): 2843–54.
   Web of Science ®Google Scholar
• T. Suksrichavalit, S. Prachayasittikul, C. Nantasenamat, C. Isarankura-Na-Ayudhya, and V. Prachayasittikul, “Copper Complexes of Pyridine Derivatives with Superoxide Scavenging and Antimicrobial Activities,” European Journal of Medicinal Chemistry 44, no. 8 (2009): 3259–65.
   PubMed Web of Science ®Google Scholar
• A. Anam, A. Abad, A. Mohd, and S. Shamsuzzaman, “Review: biologically Active Pyrazole Derivatives,” New Journal of Chemistry 41, no. 1 (2017): 16–41.
   Web of Science ®Google Scholar
• S. Delarcina Jr., C. R. Ferrari, “Process for obtaining extracts containing methylxanthine derivatives from cakes of plants of the genus Theobroma, as well as composition and use of said extract,” (US 9198848 B2 2009).
   Google Scholar
• J. P. Monteiro, M. G. Alves, P. F. Oliveira, and B. M. Silva, “Structure-Bioactivity Relationships of Methylxanthines: Trying to Make Sense of All the Promises and the Drawbacks,” Molecules 21, no. 8 (2016): 974–32.
   Web of Science ®Google Scholar
• A. M. Hayallah, W. A. Elgaher, O. I. Salem, and A. A. M. A. Alim, “Design and Synthesis of Some New Theophylline Derivatives with Bronchodilator and Antibacterial Activities,” Archives of Pharmacal Research 34, no. 1 (2011): 3–21.
   PubMed Web of Science ®Google Scholar
• O. F. Abou-Ghadir, A. M. Hayallah, S. G. Abdel-Moty, and M. A. Hussein, “Design and Synthesis of Some New Purine-Dione Derivatives of Potential anti-Inflammatory Activity,” Der Pharma Chemica 6, (2014): 199–211.
   Google Scholar
• T. V. Dunwiddie, B. J. Hoffer, and B. B. Fredholm, “Alkylxanthines Elevate Hippocampal Excitability. Evidence for a Role of Endogenous Adenosine,” Naunyn-Schmiedeberg's Archives of Pharmacology 316, no. 4 (1981): 326–30.
   PubMed Web of Science ®Google Scholar
• J. J. Kaminski, D. M. Solomon, D. J. Conn, S. C. Wong, P. Chiu, T. Massa, M. I. Siegel, and A. S. Watnick, “ Antiinflammatory activity of a series of substituted 2,3-dihydro-6-hydroxypyrimido[2,1-f]purine-4,8(1H,9H)-diones,” Journal of Medicinal Chemistry 32, no. 5 (1989): 1118–27.
   PubMed Web of Science ®Google Scholar
• P. M. P. Santos, J. P. Telo, and A. J. S. C. Vieira, “Structure and Redox Properties of Radicals Derived from One-Electron Oxidised Methylxanthines,” Redox Report: Communications in Free Radical Research 13, no. 3 (2008): 123–33.
   PubMed Web of Science ®Google Scholar
• S. R. Langman, M. C. B. L. Shohoji, J. P. Telo, A. J. S. C. Vieira, and H. M. Novais, “EPR Spectroscopy Study of the Radical Oxidation of Hydroxypurines in Aqueous Solution: Acid-Base Properties of the Derived Radicals,” Journal of the Chemical Society, Perkin Transactions 2, no. 7 (1996): 1461–5.
   Google Scholar
• A. J. S. C. Vieira, J. P. Telo, H. F. Pereira, P. F. Patrocínio, and R. M. B. Dias, “Antioxidant Effect of Naturally Occurring Xanthines on the Oxidative Damage of DNA Bases,” Journal de Chimie Physique et de Physico-Chimie Biologique 96, no. 1 (1999): 116–23.
   Google Scholar
• Ruth Arnold, David Beer, Gurdip Bhalay, Urs Baettig, Stephen P. Collingwood, Sarah Craig, Nicholas Devereux, Andrew Dunstan, Angela Glen, Sylvie Gomez, et al. “8-Aryl Xanthines Potent Inhibitors of Phosphodiesterase,” Bioorganic & Medicinal Chemistry Letters 12, no. 18 (2002): 2587–90.
   PubMed Web of Science ®Google Scholar
• L. H. Foley, P. Wang, P. Dunten, G. Ramsey, M. L. Gubler, and S. J. Wertheimer, “Modified 3-Alkyl-1, 8-Dibenzylxanthines as GTP-Competitive Inhibitors of Phosphoenolpyruvate Carboxykinase,” Bioorganic & Medicinal Chemistry Letters 13, no. 20 (2003): 3607–10.
   PubMed Web of Science ®Google Scholar
• A. M. Hayallah, G. Momekov, and M. Famulok, “Antitumor Activity of Some New 1, 3,8-Trisubstituted Purine-2, 6-Diones and 1, 3, 6-Trisubstituted Thiazolo [2, 3-f]Purine-2, 4-Diones,” Bulletin of Pharmaceutical Sciences 31, no. 2 (2008): 391–9.
   Google Scholar
• (a) R. V. Kalla, E. Elzein, Perry, T. Li, X. Palle, V. Varkhedkar, V. Gimbel, A. Maa, T. Zeng, D. Zablocki, “Novel 1,3-Disubstituted 8-(1-Benzyl-1H-Pyrazol-4-yl) Xanthines: High Affinity and Selective A2B Adenosine Receptor Antagonists,” Journal of Medicinal Chemistry 49, no. 12 (2006): 3682–92;
   Google Scholar
  (b) R. Y. Lin, B. N. Wu, Y. C. Lo, L. M. An, Z. K. Dai, Y. T. Lin, C. S. Tang, I. J. Chen, “A Xanthine-Based Epithelium-Dependent Airway Relaxant KMUP-3 (7-[2-[4-(4-Nitrobenzene)Piperazinyl]Ethyl]-1,3-Dimethylxanthine) Increases Respiratory Performance and Protects Against Tumor Necrosis Factor-Alpha-Induced Tracheal Contraction, Involving Nitric Oxide Release and Expression of cGMP and Protein Kinase GJ,” Journal of Pharmacology and Experimental Therapeutics 316, no. 2 (2006): 709–17;
   PubMed Web of Science ®Google Scholar
  (c) K. Ito, S. Lim, G. Caramori, B. Cosio, K. F. Chung, I. M. Adcock, P. J. Barnes, “A Molecular Mechanism of Action of Theophylline: Induction of Histone Deacetylase Activity to Decrease Inflammatory Gene Expression,” National Academy of Sciences of the United States of America 99, no. 13 (2002): 8921–26.
   PubMed Web of Science ®Google Scholar
• (a) G. Caramori, I. Adcock, “Pharmacology of Airway Inflammation in Asthma and COPD, Pulm,” Pharmacology & Therapeutics 16, no. 5 (2003) 247–77;
   Google Scholar
  (b) V. Dal Piaz, M. P. Giavannoni, “Phosphodiesterase 4 Inhibitors, Structurally Unrelated to Rolipram, as Promising Agents for the Treatment of Asthma and Other Pathologies,” European Journal of Medicinal Chemistry 35, no. 5 (2000): 463–80;
   PubMed Web of Science ®Google Scholar
  (c) W. F. Kiesman, J. Zhao, P. R. Conlon, J. E. Dowling, R. C. Petter, F. Lutterodt, X. Jin, G. Smits, M. Fure, A. Jayaraj, J. Kim, G. Sullivan, J. Linden, “Potent and Orally Bioavailable 8-Bicyclo[2.2.2]Octylxanthines as Adenosine A1 Receptor Antagonists,” Journal of Medicinal Chemistry 49, no. 24 (2006): 7119–31.
   PubMed Web of Science ®Google Scholar
• (a) F. V. Rao, O. A. Andersen, K. A. Vora, J. A. DeMartino, D. M. F. van Aalten, “Methylxanthine Drugs are Chitinase Inhibitors: Investigation of Inhibition and Binding Modes,” The Journal of Biological Chemistry 12, no. 37 (2006): 27278–80;
   Google Scholar
  (b) A. W. Schuttelkopf, O. A. Andersen, F. V. Rao, M. Allwood, C. Lloyd, I. M. Eggleston, D. M. F. van Aalten, “Screening-Based Discovery and Structural Dissection of a Novel Family 18 Chitinase Inhibitor,” Journal of Biological Chemistry 281, no. 37 (2006):27278–85.
   PubMed Web of Science ®Google Scholar
• T. P. T. Cushnie, B. Cushnie, and A. J. Lamb, “Alkaloids: An Overview of Their Antibacterial, Antibiotic-Enhancing and Antivirulence Activities,” International Journal of Antimicrobial Agents 44, no. 5 (2014): 377–86.
   PubMed Web of Science ®Google Scholar
• S. Perviz, H. Khan, and A. Pervaiz, “Plant Alkaloids as an Emerging Therapeutic Alternative for the Treatment of Depression,” Frontiers in Pharmacology 7, (2016): 28.
   PubMed Web of Science ®Google Scholar
• B. G. Benfey, “Theophylline and Phenylephrine Effects on Cardiac Relaxation,” British Journal of Pharmacology 59, no. 1 (1977): 75–81.
   PubMed Web of Science ®Google Scholar
• G. Yu, V. Maskray, S. Jackson, C. Swift, and B. Tiplady, “A Comparison of the Central Nervous System Effects of Caffeine and Theophylline in Elderly Subjects,” British Journal of Clinical Pharmacology 32, no. 3 (1991): 341–45.
   PubMed Web of Science ®Google Scholar
• K. F. Rabe, H. Magnussen, and G. Dent, “Theophylline and Selective PDE Inhibitors as Bronchodilators and Smooth Muscle Relaxants,” European Respiratory Journal 8, no. 4 (1995): 637–42.
   PubMed Web of Science ®Google Scholar
• M. Bell, E. Jackson, Z. Mi, J. McCombs, and J. Carcillo, “Low-Dose Theophylline Increases Urine Output in Diuretic-Dependent Critically ILL Children,” Intensive Care Medicine 24, no. 10 (1998): 1099–105.
   PubMed Web of Science ®Google Scholar
• D. Boison, “Methylxanthines, Seizures and Excitotoxicity,” Handbook of Experimental Pharmacology 200 (2011): 251–66.
   PubMedGoogle Scholar
• L. C. Foukas, N. Daniele, C. Ktori, K. E. Anderson, J. Jensen, and P. R. Shepherd, “Direct Effects of Caffeine and Theophylline on p110 Delta and Other Phosphoinositide 3-Kinases. Differential Effects on Lipid Kinase and Protein Kinase Activities,” Journal of Biological Chemistry 277, no. 40 (2002): 37124–130.
   PubMed Web of Science ®Google Scholar
• K. Sugimura, and A. Mizutani, “The Inhibitory Effect of Xanthine Derivatives on Alkaline Phosphatase in the Rat Brain,” Histochemistry 61, no. 2 (1979): 131–37.
   PubMedGoogle Scholar
• Y. Cao, J. Wei, L. Zou, T. Jiang, G. Wang, L. Chen, L. Huang, F. Meng, L. Huang, N. Wang, X. Zhou, et al. “Ruxolitinib in Treatment of Severe Coronavirus Disease 2019 (COVID-19): A Multicenter, Single-Blind, Randomized Controlled Trial,” Journal of Allergy and Clinical Immunology 146, no. 1 (2020): 137–46.
   PubMed Web of Science ®Google Scholar
• J. Glogowski, D. R. Danforth, and A. Ciereszko, “Inhibition of Alkaline Phosphatase Activity of Boar Semen by Pentoxifylline, Caffeine, and Theophylline,” Journal of Andrology 23, no. 6 (2002): 783–92.
   PubMedGoogle Scholar
• V. Papesch, and E. F. Schroeder, “Synthesis of 1-Mono-and 1, 3-di-Substituted 6-Aminouracils, Diuretic Activity,” The Journal of Organic Chemistry 16, no. 12 (1951): 1879–90.
   Web of Science ®Google Scholar
• A. R. Saundane, K. Vijaykumar, M. Yarlakatti, W. Prabhaker, and A. V. Vaijinath, “Synthesis and Biological Activities of Some Indole Analogues Containing Pyridine, Pyridopyrimidine and Pyranonapthyridine Systems,” Heterocyclic Letters 1, no. 4 (2011): 339–50.
   Google Scholar
• F. F. Blicke, and H. C. Godt, “Reactions of 1,3-Dimethyl-5,6-Diaminouracil,” Journal of the American Chemical Society 76, no. 10 (1954): 2798–800.
   Web of Science ®Google Scholar
• H. Ben Ammar, M. T. Kaddachi, and P. H. Kahn, “Conversion of Malononitrile into 2-Cyanomethyl Compounds,” Journal in Physics and Chemistry 9 (2003): 137–39.
   Google Scholar
• C. L. Gibson, S. La Rosa, and C. Suckling, “A Prototype Solid Phase Synthesis of Pteridines and Related Heterocyclic Compounds,” Organic & Biomolecular Chemistry 1, no. 11 (2003): 1909–18.
   PubMed Web of Science ®Google Scholar
• A. M. Hayallah, and M. Famulok, “Synthesis of New 1, 3, 8-Trisubstituted Purine-2, 6-Diones and 1, 3, 6-Trisubstituted Thiazolo [2, 3-f] Purine-2, 4-Diones,” Heterocycles 74, no. 1 (2007): 369–82.
   Google Scholar
• A. R. Saundane, K. Vijaykumar, A. V. Vaijinath, and W. Prabhaker, “Synthesis, Antimicrobial and Antioxidant Activities of Some New Indole Derivatives Containing Pyridopyrimidine and Pyrazolopyridine Moieties,” Medicinal Chemistry Research 22, no. 2 (2013): 806–17.
   Web of Science ®Google Scholar
• A. R. Saundane, K. Vijaykumar, and A. V. Vaijinath, “Synthesis of Novel 2-Amino-4-(5'-Substituted 2'-Phenyl-1H-Indol-3'-yl)-6-Aryl-4H-Pyran-3-Carbonitrile Derivatives as Antimicrobial and Antioxidant Agents,” Bioorganic & Medicinal Chemistry Letters 23, no. 7 (2013): 1978–84.
   PubMed Web of Science ®Google Scholar
• K. A. Toharo, A. Toharo, Foundation of Microbiology (Dubuque: W.C. Brown Publisher, 1993), edition, 3, 326.
   Google Scholar
• National Committee for Clinical Laboratory Standards (NCCLS), Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts: Approved Standard M27-A (Villanova, PA: NCCLS, 1997).
   Google Scholar
• National Committee for Clinical Laboratory Standards (NCCLS), Standard methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 2nd ed. Approved standard M7-A2 (Villanova, PA: National Committee for Clinical Laboratory Standards, 1990).
   Google Scholar
• National Committee for Clinical Laboratory Standards (NCCLS), Performance standards for antimicrobial susceptibility testing; ninth informational supplement. M100-S9 (Villanova, PA: National Committee for Clinical Laboratory Standards, 1999).
   Google Scholar
• V. D. Warner, J. D. Musto, J. N. Sane, K. H. Kim, and G. L. Grunewald, “Quantitative Structure-Activity Relationships for 5-Substituted 8-Hydroxyquinolines as Inhibitors of Dental Plaque,” Journal of Medicinal Chemistry 20, no. 1 (1977): 92–96.
   PubMed Web of Science ®Google Scholar
• R.V. Goering, H.M. Dockrell, M. Zuckerman, P.L. Chiodini, I.M. Roitt, The Bacteria. Mims's Medical Microbiology, 5th ed. (China: Elsevier, 2013), 7.
   Google Scholar
• Vaijinath, A. Verma, A. R. Saundane, S. M. Rajkumar, Raju. Shamro, and K. Vijaykumar, “Synthesis, Biological Evaluation and Docking Studies of Some New Indolyl-Pyridine Containing Thiazolidinone and Azetidinone Analogs,” Polycyclic Aromatic Compounds (2020): 1-15. 10.1080/10406638.2020.1786706.
   Web of Science ®Google Scholar
• T. Mosmann, “Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays,” Journal of Immunological Methods 65, no. 1–2 (1983): 55–63.
   PubMed Web of Science ®Google Scholar
• V. Lobo, A. Patil, A. Phatak, and N. Chandra, “Free Radicals, Antioxidants and Functional Foods: Impact on Human Health,” Pharmacognosy Reviews 4, no. 8 (2010): 118–26.
   PubMedGoogle Scholar
• L. A. Pham-Huy, H. He, and C. Pham-Huy, “Free Radicals, Antioxidants in Disease and Health,” International Journal of Biomedical Science 4, no. 2 (2008): 89–96.
   PubMedGoogle Scholar
• (a) B. Halliwell, J. M. C. Gutteridge, Free Radicals in Biology and Medicine, 4th ed. (Clarendon: Oxford, UK, 2007);
   Google Scholar
  (b) A. M. Papas, Antioxidant (CRC Press: Boca Raton, 1999);
   Google Scholar
  (c) B. Halliwell, “Reactive Species and Antioxidants. Redox Biology is a Fundamental Theme of Aerobic Life,” Journal of Plant Physiology 141 (2006): 312–22;
   Google Scholar
  (d) O. Firuzi, R. Miri, M. Tavakkoli, L. Saso, Antioxidant Therapy: Current Status and Future Prospects,” Current Medicinal Chemistry, 18, no. 25 (2011): 3871–88;
   PubMed Web of Science ®Google Scholar
  (e) S. Cuzzocrea, D. P. Riley, A. P. Caputi, D. Salvemini, “Antioxidant Therapy: A New Pharmacological Approach in Shock, Inflammation, and Ischemia/Reperfusion Injury,” Pharmacological Reviews 53, no. 1 (2001): 135–59.
   Google Scholar
• B. Sagar Kedare, and R. P. Singh, “Genesis and Development of DPPH Method of Antioxidant Assay,” Journal of Food Science and Technology 48, no. 4 (2011): 412–22.
   PubMed Web of Science ®Google Scholar
• A. Biswal, R. Venkataraghavan, and V. Pazhamalai, “Molecular Docking of Various Bioactive Compounds from Essential Oil of Trachyaspermum Ammi against the Fungal Enzyme Candidapepsin-1,” Journal of Applied Pharmaceutical Science 9, no. 5 (2019) 21–32.
   Google Scholar
• A. R. Biswal, K. Mirunalini, P. Jayshree, and V. Pazhamalai. “Molecular Docking Analysis of Bioactive Compounds of Acacia Concinna against Fungal Protein,” Journal of Pharmaceutical Sciences and Research 11, no. 4 (2019): 1216–22.
   Google Scholar
• M. Vieth, and J. J. Sutherland, “Dependence of Molecular Properties on Proteomic Family for Marketed Oral Drugs,” Journal of Medicinal Chemistry 49, no. 12 (2006): 3451–53.
   PubMed Web of Science ®Google Scholar
• A. Daina, O. Michielin, and V. Zoete, “ SwissADME: A Free Web Tool to Evaluate Pharmacokinetics, Drug-Likeness and Medicinal Chemistry Friendliness of Small Molecules,” Scientific Reports 7 (2017): 42717.
   PubMed Web of Science ®Google Scholar
• F. Cheng, W. Li, Y. Zhou, J. Shen, Z. Wu, G. Liu, P. W. Lee, and Y. Tang, “admetSAR: A Comprehensive Source and Free Tool for Assessment of Chemical ADMET Properties,” Journal of Chemical Information and Modeling 52, no. 11 (2012): 3099–105.
   PubMed Web of Science ®Google Scholar
• T. Hatano, H. Kagawa, T. Yasuhara, and T. Okuda, “Two New Flavonoids and Other Constituents in Licorice Root: Their Relative Astringency and Radical Scavenging Effects,” Chemical & Pharmaceutical Bulletin 36, no. 6 (1988): 2090–97.
   PubMed Web of Science ®Google Scholar