The anticancer potential of various substituted pyridazines and related compounds

  • Authors

    • Mohammad Asif GRD(PG)IMT, RAJPUR, DEHRADUN
    2014-09-15
    https://doi.org/10.14419/ijac.v2i2.2661

  • Pyridazine nucleus exhibited immense pharmacological activities. Pyridazine nucleus is present in various compounds that possess remarkable pharmacological activities. Various pyridazinone compounds have antitumor activity. Some of them pyridazinone derivatives bearing different moieties were exhibited excellent anticancer activity toward human cancer cell lines. They showed remarkable activity against leukemia, non-small cell lung cancer, colon, central nervous system, melanoma, ovarian and breast cancer cell lines. These compounds were act by different mechanism.

    Keywords: Pyruvate Kinase; Anti-Cancer; Pyridazines; Biological Activities; Cytotoxicity.

  • References

    1. Abd El-Ghaffar NF, Mohamed MK, Kadah MS, Radwan AM, Said GH, Abdel Al SN (2011) Synthesis and anti-tumor activities of some new pyridazinones containing the 2-phenyl-1H-indolyl moiety. J Chem Pharm Res 3(3): 248-259.
    2. Abdelrazek FM, Michael FA, Mohamed AE. (2006) Synthesis and molluscicidal activity of some 1,3,4-triaryl-5-chloropyrazole, pyrano[2,3-c]pyrazole, pyrazolylphthalazine and pyrano[2,3-d]thiazole derivatives. Arch Pharm (Weinheim) 339(6): 305-12. http://dx.doi.org/10.1002/ardp.200500259.
    3. Akinaga S, Sugiyama K, Akiyama, T (2000) UCN-01 (7-Hydroxystaurosporine) and Other Indolocarbazole Compounds: A New Generation of Anti-Cancer Agents for the New Century? Anti-Cancer Drug Des 15: 43-52.
    4. Allerton CM, Andrews MD, Blagg J, Ellis D, Evrard E, Green MP, Liu KK, McMurray G, Ralph M, Sanderson V, Ward R, Watson L (2009) Design and synthesis of pyridazinone-based 5-HT(2C) agonists. Bioorg Med Chem Lett 19(19): 5791-5. http://dx.doi.org/10.1016/j.bmcl.2009.07.136.
    5. Asif M (2012). Some Recent Approaches of Biologically Active Substituted Pyridazine and Phthalazine Drugs. Curr Med Chem 19(18): 2984-2991. http://dx.doi.org/10.2174/092986712800672139.
    6. Asif M, Singh A (2010) Exploring Potential, Synthetic Methods and General Chemistry of Pyridazine and Pyridazinone: A Brief Introduction. Inter J Chem Tech Res 2(2): 1112-1128.
    7. Bansal R, Kumar D, Carron R, de la Calle C (2009)Synthesis and vasodilatory activity of some amide derivatives of 6-(4-carboxymethyloxyphenyl)-4,5-dihydro-3(2H)-pyridazinone. Eur J Med Chem 44(11): 4441-7. http://dx.doi.org/10.1016/j.ejmech.2009.06.006.
    8. Bashir R, Yaseen S, Ovais S, Ahmad S, Hamid H, Alam MS, Samim M, Javed K. (2010) Synthesis and biological evaluation of some novel sulfamoylphenyl-pyridazinone as anti-inflammatory agents (Part-I). J Enz Inhib & Med Chem 25(2): 266–271.
    9. Batra JJK, Powers LJ, Hess FD, Hamel E (1986) Derivatives of 5,6-Diphenylpyridazin-3-one: Synthetic Antimitotic Agents Which Interact with Plant and Mammalian Tubulin at a New Drug-bindingSite. Cancer Research, 46: 1889-1893.
    10. Batra JK, Jurd, L, Hamel, E. (1985) Structure-function studies with deriva tives or6-benzyl-l,3-benzodioxole, a new class of synthetic compounds which inhibit tubulin polymerization and mitosis. Mol Pharmacol 27: 94-102.
    11. Block HJ, Beale JM (2004) Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical chemistry, 11th ed.; Lippincott Williams & Wilkins: Baltimore, MD, USA, 390-394.
    12. Boyd MR (1997) In Cancer Drug Discovery and Development; Teicher, B.A., Ed.; Humana Press: Totowa, NJ, USA, 2: 23-43.
    13. Boyd MR, Paull KD (1995) some practical considerations and applications of the national cancer institute in vitro anticancer drug discovery screen. Drug Dev Res, 34: 91-109. http://dx.doi.org/10.1002/ddr.430340203.
    14. Brana MF, Anorbe L, Tarrason G, Mitjans F, Piulats J (2001) Synthesis and Biological Evaluation of Novel Bisindolylmaleimides That Inhibit Vascular Endothelial Cell Proliferation. Bioorg Med Chem 11: 2701-2703. http://dx.doi.org/10.1016/S0960-894X (01)00535-2.
    15. Brana MF, Cacho M, Garcıa ML, Mayoral EP, Lopez B, de Pascual-Teresa B, Ramos A, Acero N, Llinares F, Munoz-Mingarro D, Lozach O, Meijer L (2005). Pyrazolo[3,4-c]pyridazines as Novel and Selective Inhibitors of Cyclin-Dependent Kinases. J Med Chem 48: 6843-6854. http://dx.doi.org/10.1021/jm058013g.
    16. Buchman R, Scozzie J A, Ariyan ZS, Heilman RD, Rippin DJ, Pyne WJ, Powers LJ (1980) Antihypertensive 5,6-diarylpyridazin-3-ones. J Med Chem 23: 1398-1405. http://dx.doi.org/10.1021/jm00186a021.
    17. Chabner BA, Amrein PC, Druker BJ, Michaelson MD, Mitsiades CS, Goss PE, Ryan DP, Ramachandra S, Richardson PG, Supko JG, Wilson WH (2005) Antineoplastic Agents. In Goodman & Gilman's the Pharmacological Basis of Therapeutics, 11th ed.; Brunton, L.L., Lazo, J.S., Parker, K.L., Eds.; Mc Graw-Hill Professional: New York, NY, USA, pp. 1315-1403.
    18. Cignarella G, Barlocco D, Curzu MM, Pinna GA, Cazzulani P, Cassin M, Lumachi B (1990) Synthesis and pharmacological evaluation of 4,4a-dihydro-5H-[1]benzopyrano[4,3-c]pyridazin-3(2H)-ones bioisosters of antihypertensive and antithrombotic benzo[H]cinnolinones. Eur J Med Chem 25: 749-756. http://dx.doi.org/10.1016/0223-5234 (90)90194-8.
    19. Cignarella G, Barlocco D, Pinna GA, Loriga M, Curzu MM, Tofanetti O, Germini M, Cazzulani P, Cavalletti E (1989) Synthesis and biological evaluation of substituted benzo[H]cinnolinones and 3H-benzo[6,7]cyclohepta[1,2-c]pyridazinones: higher homologues of the antihypertensive and antithrombotic 5H-indeno[1,2-c]pyridazinones. J Med Chem 32: 2277-2282. http://dx.doi.org/10.1021/jm00130a009.
    20. Costantino L, Rastelli G, Vescovini K, Cignarella G, Vianello P, Corso AD, Cappiello M, Mura U, Barlocco D (1996) Synthesis, activity, and molecular modeling of a new series of tricyclic pyridazinones as selective aldose reductase inhibitors. J Med Chem 39: 4396-4405. http://dx.doi.org/10.1021/jm960124f.
    21. Costas T, Besada P, Piras A, Acevedo L, Ya-ez M, Orallo F, Laguna R, Terán C (2010) New pyridazinone derivatives with vasorelaxant and platelet antiaggregatory activities. Bioorg & Med Chem Lett, 20(22): 6624-6627. http://dx.doi.org/10.1016/j.bmcl.2010.09.031.
    22. Costas T, Besada P, Piras A, Acevedo L, Ya-ez M, Orallo F, Laguna R, Terán C (2010) New pyridazinone derivatives with vasorelaxant and platelet antiaggregatory activities. Bioorg & Med Chem Lett, 20(22): 6624-6627. http://dx.doi.org/10.1016/j.bmcl.2010.09.031.
    23. Devita VT Jr, Hellman S, Rosenberg SA, editors (2005) Cancer Principles & Practice of Oncology. 7. Lippincott Williams & Wilkins; Philadelphia.
    24. Faidallah HM, Khan KA, Makki MSI (2011). Synthesis and Biological Evaluation of New Fused Isoxazolo[4,5-d] Pyridazine Derivatives. J Chinese Chem Soc 58: 191-198. http://dx.doi.org/10.1002/jccs.201190076.
    25. Fidesser E, Haider N, Jbara R (2001) Convenient Synthesis of New 3-Aminocarbazole and Pyrimido[5,4-b]carbazole Derivatives. ARKIVOC, 2: 133–139.
    26. Fidler IJ (2003). The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer 3: 453-458. http://dx.doi.org/10.1038/nrc1098.
    27. Gilchrest BA, Eller MS (2009) Cancer therapeutics: Smart and smarter. Drugs Future, 34: 205-216. http://dx.doi.org/10.1358/dof.2009.034.03.1336071.
    28. Grella GE, Cabras MC, Murineddu G, Pau A, Pinna GA (2003) Synthesis and cytotoxicity of substituted 2-benzylnaphth [2, 3-d]imidazoles. Eur J Pharm Sci 20: 267-272. http://dx.doi.org/10.1016/S0928-0987 (03)00197-0.
    29. Gribble G W (1990) the Alkaloids, Vol. 39, ed. by Brossi A, Academic Press, New York, pp. 239-352.
    30. [30] Haider N, Kabicher T, Käferböck J, Plenk A (2007) Synthesis and In-vitro Antitumor Activity of 1-[3-(Indol-1-yl)prop-1-yn-1-yl]phthalazines and Related Compounds. Molecules 12: 1900-1909. http://dx.doi.org/10.3390/12081900.
    31. Haider N (2002) Pyridazine-Fused Carbazoles: Synthesis, Reactivity, and Antitumor Activity. J Heterocycl Chem 39: 511–521. http://dx.doi.org/10.1002/jhet.5570390307.
    32. Haider N, Jbara R, Khadami F, Wanko R (1998) Synthesis of Pyridazino[4,5-b]carbazoles as Potential Antineoplastic Agents. Heterocycles 48: 1609–1622. http://dx.doi.org/10.3987/COM-98-8217.
    33. Haider N, Käferböck J (2004) Intramolecular [4+2] cycloaddition reactions of indolylalkylpyridazines: synthesis of annulated carbazoles. Tetrahedron 60: 6495–6507. http://dx.doi.org/10.1016/j.tet.2004.06.008.
    34. Haider N, Käferböck J, Mátyus P (1999) Diels-Alder Reaction of Pyrano[3,4-b]indolones with an Electron-Deficient Pyridazinone: a New Pathway to Carbazole-Fused Pyridazines. Heterocycles, 51: 2703–2710. http://dx.doi.org/10.3987/COM-99-8695.
    35. Haider N, Sotelo E (2002) 1, 5-Dimethyl-6H-pyridazino [4, 5-b]carbazole, a 3-Aza Bioisoster of the Antitumor Alkaloid Olivacine. Chem Pharm Bull 50(11): 1479-1483. http://dx.doi.org/10.1248/cpb.50.1479.
    36. Hamel E (1984) Antimitotic drugs and tubulin-nucleotide interactions. In. R. I. Glazer (ed.), Developments in Cancer Chemotherapy, pp. 131-164.Boca Raton, FL: CRC Press.
    37. Hamel E, Lin CM (1983) Interactions of combretastatin, a new plant derived antimitotic agent, with tubulin. Biochem. Pharmacol, 32: 3864-3867. http://dx.doi.org/10.1016/0006-2952 (83)90163-6.
    38. Hamel E, Lin CM (1984) Guanosine 5'-O-(3-thiotriphosphate), a potent nucleotide inhibitor of microtubule assembly. J. Biol. Chem., 259: 11060-11069.
    39. Husain A, Drabu S, Kumar N, Alam MM, Ahmad A (2011) Synthesis and biological evaluation of some new pyridazinone derivatives. J En Inhib & Med Chem 26(5): 742-748. http://dx.doi.org/10.3109/14756366.2010.548810.
    40. Huwe A, Mazitschek R, Giannis A (2003) Small Molecules as Inhibitors of Cyclin-Dependent Kinases. Angew Chem, Int. Ed. 42: 2122-2138. http://dx.doi.org/10.1002/anie.200200540.
    41. Jiang JK, Boxer MB, Vander Heiden MG, Shena M, Skoumbourdis AP, Southall N, Veith H, Leister W, Austin CP, Parke HW, Inglese J, Cantley LC, Auld DS, Thomas CJ (2010). Evaluation of Thieno[3,2-b]pyrrole[3,2-d]pyridazinones as Activators of the Tumor Cell Specific M2 Isoform of Pyruvate. Kinase. Bioorg & Med Chem Lett 20 (11): 3387–3393. http://dx.doi.org/10.1016/j.bmcl.2010.04.015.
    42. Knockaert M, Greengard P, Meijer L (2002) Pharmacological Inhibitors of Cyclin-Dependent Kinases. Trends Biochem Sci 23: 417-425.
    43. Luduena RF, Fellous A, McManus L, Jordan MA, Nunez J (1984) Contrasting roles of tau and microtubule-associated protein 2 in the vinblas tine-induced aggregation ofbrain tubulin. J Biol Chem 259: 1289-12898.
    44. Malinka W (2001) Synthesis of some pyrrolo[3,4-d]pyridazinones and their preliminary anticancer, antimycobacterial and CNS screening. Pharmazie 56(5): 384-9.
    45. Malinka W, Redzicka A, Lozach O (2004). New derivatives of pyrrolo[3,4-d] pyridazinone and their anticancer effects. Farmaco 59(6): 457-62. http://dx.doi.org/10.1016/j.farmac.2004.03.002.
    46. Malumbre M, Barbacid M (2001) To Cycle or Not To Cycle: A Critical Decision in Cancer. Nat. Rev. Cancer 1: 222-231. http://dx.doi.org/10.1038/35106065.
    47. McGrath CF, Pattabiraman N, Kellogg GE, Lemcke T, Kunick C, Sausville EA, Zaharevitz D W, Gussio R (2005) Homology Model of the CDK1/Cyclin B Complex. J Biomol Struct Dyn 22: 493-502. http://dx.doi.org/10.1080/07391102.2005.10531227.
    48. Meijer L, Frajolet M, Greengard P (2004) Pharmacological inhibitors of glycogen synthase kinase-3. Trends Pharmacol Sci 25: 471-480. http://dx.doi.org/10.1016/j.tips.2004.07.006.
    49. Mizens M, Brown WR, Killeen JC Jr, Ignatoski JA (1985) Subchronic feeding study in rats with five pyridazinone compounds structurally related to DS-29399. Toxicologist, 5: 60.
    50. Mizens M, Brown WR, Laveglia J, Killeen JC Jr, Ignatoski JA (1984) Combined 30-day feeding study and one-generation reproduction study in rats with ethyl 5-cyano-3,4-diphenyl-6-oxo-1-6HJ-pyridazineacetate (DS 29399). Toxicologist 4: 17.
    51. Monks A, Scudiero D, Skehan P, Shoemaker R, Paull KD, Vistica D, Hose C, Langley J, Cronise P, Vaigro-Wolff A (1991) Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J Natl Cancer Inst 83: 757-766. http://dx.doi.org/10.1093/jnci/83.11.757.
    52. Murineddu G, Cignarella G, Chelucci G, Loriga G, Pinna GA (2002) Synthesis and cytotoxic activities of pyrrole[2,3-d]pyridazin-4-one derivatives. Chem Pharm Bull 50: 754-759. http://dx.doi.org/10.1248/cpb.50.754.
    53. Norbert H, Eddy S (2002) 1, 5-Dimethyl-6H-pyridazino[4,5-b]carbazole, a 3-Aza Bioisoster of the Antitumor Alkaloid Olivacine. Chem Pharm Bull 50(11): 1479-1483. http://dx.doi.org/10.1248/cpb.50.1479.
    54. Pau A, Asproni B, Boatto G, Grella GE, De Caprariis P, Costantino L, Pinna GA (2004) Synthesis and aldose reductase inhibitory activities of novel thienocinnolinone derivatives. Eur J Pharm Sci 21: 545-552. http://dx.doi.org/10.1016/j.ejps.2003.12.005.
    55. Pau A, Murineddu G, Asproni B, Murruzzu C, Grella GE, Pinna GA, Curzu MM, Marchesi I, Bagella L (2009) Synthesis and Cytotoxicity of Novel Hexahydrothienocycloheptapyridazinone Derivatives. Molecules 14, 3494-3508. http://dx.doi.org/10.3390/molecules14093494.
    56. Paull KD, Shoemaker RH, Hodes L, Monks A, Scudiero DA, Rubinstein L, Plowman J, Boyd MR (1989) Display and analysis of patterns of differential activity of drugs against human tumor cell lines: development of mean graph and COMPARE algorithm. J Natl Cancer Inst 81 1088-1092. http://dx.doi.org/10.1093/jnci/81.14.1088.
    57. Pinna GA, Curzu MM, Murineddu G, Chelucci G, Cignarella G, Menta E, Krell HW, Rastelli G, Ferrari AM (2000) Preparation of thieno[3,2-H]cinnolinones as matrix metalloproteinase inhibitors. Arch Pharm Pharm Med Chem 333: 37-47. http://dx.doi.org/10.1002/ (SICI) 1521-4184(200002)333:2/3<37: AID-ARDP37>3.0.CO; 2-V.
    58. Pinna GA, Murineddu G, Murruzzu C, Zuco V, Zunino F, Cappelletti G, Artali R, Cignarella G, Solano L, Villa S (2009) Synthesis, modelling, and antimitotic properties of tricyclic systems characterised by a 2-(5-Phenyl-1H-pyrrol-3-yl)-1,3,4-oxadiazole moiety. Chem Med Chem 4: 998-1009. http://dx.doi.org/10.1002/cmdc.200800428.
    59. Pinna GA, Salis E, Berta D, Gavini E (1997) Synthesis and pharmacological evaluation of 4amethyl-4,4a,5,6-tetrahydrothieno[2,3-h]cinnolin-3(2H)-ones. Farmaco 52: 29-33.
    60. Pirisi MA, Murineddu G, Mussinu JM, Pinna GA (2002) Synthesis and cytotoxicity evaluation of thiophene analogues of 1-methyl-2, 3-bis(hydroxymethyl)benzo[g]indole bis[N-(2- propyl)carbamate]. Farmaco 57: 331-335 http://dx.doi.org/10.1016/S0014-827X(02)01201-6.
    61. Rakib EM, Abouricha S, Hannioui A, Benchat N, Ait M'barek L, Zyad A (2006) Synthesis and in vitro Cytotoxicity Studies of Novel Triazolo[4,3-b]pyridazinones. J Iranian Chem Soc 3(3): 2006, 272-276. http://dx.doi.org/10.1007/BF03247219.
    62. Rathish IG, Javed K, Ahmad S, Bano S, Alam MS, Akhter M, Pillai V, Ovais S, Samim M (2012). Synthesis and evaluation of anticancer activity of some novel 6-aryl-2-(p-sulfamylphenyl)-pyridazin-3(2H)-ones. Eur J Med Chem, 49: 304-309. http://dx.doi.org/10.1016/j.ejmech.2012.01.026.
    63. Sedlacek HH, Czech J, Naik R, Kaur G, Worland P, Losiewicz M, Parker B, Carlson B, Smith A, Senderowicz A, Sausville E (1996) Flavopiridol (L86-8275, NSC-649890), a New Kinase Inhibitor for Tumor Therapy. Int J Oncol 9: 1143-1168.
    64. Senderowicz AM, Headlee D, Stinson SF, Lush RM, Kalil N, Villalba L, Hill K, Steinberg SM, Figg WD, Tompkins A, Arbuck SG, Sausville EA (1998) Phase I Trial of Continuous Infusion Flavopiridol, a Novel Cyclin-Dependent Kinase Inhibitor, in Patients with Refractory Neoplasms. J Clin Oncol 16: 2986-2999.
    65. Sielecki TM, Boylan JF, Benfield PA, Trainor GL (2000) Cyclin Dependent Kinase Inhibitors: Useful Targets in Cell Cycle Regulation. J Med Chem 43, 1-18. http://dx.doi.org/10.1021/jm990256j.
    66. Silverman RJ (2004) the Organic Chemistry of Drug Design and Drug Action, 2nd ed.; Elsevier Academic Press: Burlington, MA, USA, 13-14.
    67. Sims PA, Wong CF, McCammon JA (2003) A Computational Model of Binding Thermodynamics: The Design of Cyclin-Dependent Kinase 2 Inhibitors. J Med Chem 46: 3314- 3325. http://dx.doi.org/10.1021/jm0205043.
    68. Spreitzer H, Pichler A, Holzer W, Kratzel M, Slanz R, Koulouri A, Krenn P, Parrer U, Szieber P (2001) Synthesis of azanaphthoquinone annelated pyrroles. Heterocycles 54, 111–121. http://dx.doi.org/10.3987/COM-98-8401.
    69. Spreitzer H, Puschmann C (2007) Synthesis of Anticancer Compounds, I, "Dual Function" Antitumor Agents Based on Bioreduction and DNA-Alkylation. Monatsh Chem 138: 517–522. http://dx.doi.org/10.1007/s00706-007-0604-7.
    70. Staal GEJ, Rijksen G (1991) Biochemical and molecular aspects of selected cancers. Pretlow, TG; Pretlow, TP., editors. Academic Press; San Diego p. 313 http://dx.doi.org/10.1016/B978-0-12-564498-3.50013-3.
    71. Teague SJ (2003) Implications of Protein Flexibility for Drug Discovery. Nat Rev Drug Discovery 2: 527-541. http://dx.doi.org/10.1038/nrd1129.
    72. Unsal tan O, Ozadali K, Yes O¸ Ilyurt, Kayir H, Uzbay T, Balkan A (2011) Synthesis and evaluation of the analgesic activity of some new isoxazolo[4,5-d]pyridazin-4(5H)-one derivatives. Turk J Chem 35: 121-130.
    73. Wang T, Dong Y, Wang LC, Xiang BR, Chen Z, Qu LB (2008). Design, synthesis and structure-activity relationship studies of 6-phenyl-4, 5-dihydro-3(2H)-pyridazinone derivatives as cardiotonic agents. Arzneimittelforschung 58(11): 569-73.
    74. Ward, R. W.; Witherington, J. Pyrazolopyridazine Derivatives, Process for Preparation and Use for the Inhibition of GSK-3. WO03080616, 2003.
    75. Witherington J, Bordas V, Garland SL, Hickey DMB, Ife RJ, Liddle J, Saunders M, Smith DG, Ward RW (2003) 5-Aryl-pyrazolo[3,4-b]pyridines: Potent Inhibitors of Glycogen Synthase Kinase-3 (GSK-3). Bioorg & Med Chem Lett 13: 1577-1580. http://dx.doi.org/10.1016/S0960-894X (03)00134-3.
    76. Zhou G, Ting PC, Aslanian R, Cao J, Kim DW, Kuang R, Lee JF, Schwerdt J, Wu H, Herr RJ, Zych AJ, Yang J, Lam S, Wainhaus S, Black TA, McNicholas PM, Xu Y, Walker SS (2011). SAR studies of pyridazinone derivatives as novel glucan synthase inhibitors. Bioorg Med Chem Lett. 21(10): 2890-3. http://dx.doi.org/10.1016/j.bmcl.2011.03.083.

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    Asif, M. (2014). The anticancer potential of various substituted pyridazines and related compounds. International Journal of Advanced Chemistry, 2(2), 148-161. https://doi.org/10.14419/ijac.v2i2.2661