Efficient Synthesis of a New Class of N-Nucleosides of 4H-Thiochromeno[2,3-d]pyrimidine-10-Sulfone as Potential Anticancer and Antibacterial Agents

DOI: 10.4236/ijoc.2013.33A003   PDF   HTML     3,063 Downloads   5,041 Views   Citations


A highly practical and efficient preparation of 6-methy-4H-thiochromene and 7-methyl-thiochromene[2,3-d]pyrimidine derivatives was developed via a multi-component reaction of 3-methyl-thiophenol (1), aldehydes (2), and malononitrile (3). A series of pyrimidine nucleoside, thiochromene[2,3-d]pyrimidine and thiochromene[2,3-d]pyrimidine-10-sulfone was efficiently obtained. These hybrid compounds were evaluated as potential antibacterial and anticancer agents and showed encouraging biological activities. Some of these derivatives showed broad-spectrum antitumour activity against the nine tumour subpanels tested, and demonstrated significant activity in the in vitro antitumour screening expressed by MG-MID log10GI50 value of -4.55, -4.67 and -4.73 of compounds 9a, 9b and 9c, respectively.

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A. Alshammari, A. El-Gazzar and H. Hafez, "Efficient Synthesis of a New Class of N-Nucleosides of 4H-Thiochromeno[2,3-d]pyrimidine-10-Sulfone as Potential Anticancer and Antibacterial Agents," International Journal of Organic Chemistry, Vol. 3 No. 3A, 2013, pp. 15-27. doi: 10.4236/ijoc.2013.33A003.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] E. De Clercq, D. Desgranges, P. Herdewijin, I. S. Shim, A. S. Jones, M. J. Mclean and R. T. Walker, “Synthesis and Antiviral Activity of (E)-5-(2-Bromovinyl)uracil and (E)-5-(2-Bromovinyl)uridine,” Journal of Medicinal Chemistry, Vol. 29, No. 2, 1986, pp. 213-217.
[2] T. S. Lin, J. T. Guo, R. F. Schinazi, C. K. Chu, J. N. Xiang and W. H. Prusoff, “Synthesis and Antiviral Activity of Various 3’-Azido Analogues of Pyrimidine Deoxyribonucleosides against Human Immunodeficiency Virus (HIV-1, HTLV-III/LAV),” Journal of Medicinal Chemistry, Vol. 31, No. 2, 1988, pp. 336-340.
[3] C. Heidelberger, D. D. King and D. Shugar, “Antiviral Agents in Pharmacology and Therapeutics,” Pergamon, Oxford, 1979, p. 472.
[4] F. W. Hobbs, “Palladium-Catalyzed Synthesis of Alkynylamino Nucleosides: A Universal Linker for Nucleic Acids,” The Journal of Organic Chemistry, Vol. 54, No. 14, 1989, pp. 3420-3422.
[5] B. C. Froehler, S. Wadwani, J. J. Terhorst and S. K. Gerrad, “Oligodeoxynucleotides Containing C-5 Propyne Analogs of 2′-Deoxyuridine and 2′-Deoxycytidine,” Tetrahedron Letters, Vol. 33, No. 37, 1992, pp. 5307-5307.
[6] A. W. Taylor and D. K. Dean, “A New Synthesis of Thioflavones,” Tetrahedron Letters, Vol. 29, No. 15, 1988, pp. 1845-1848. http://dx.doi.org/10.1016/S0040-4039(00)82060-2
[7] S. W. Schneller, “Thiochromanones and Related Compounds,” Advances in Heterocyclic Chemistry, Vol. 18, 1975, pp. 59-97.
[8] P. Kumar, A. T. Rao and B. Pandey, “An Efficient Approach to the Synthesis of 4H-1-Benzo-Thiopyran-4-Ones via Intramolecular Wittig Reaction,” Journal of the Chemical Society, Chemical Communications, No. 21, 1992, pp. 1580-1584. http://dx.doi.org/10.1039/c39920001580
[9] P. Kumar and M. S. Bodas, “A New Synthesis of 4H-1-Benzothiopyran-4-Ones Using (Trimethylsilyl)-Methylenetriphenylphosphorane,” Tetrahedron, Vol. 57, 2001, pp. 9755-9758.
[10] A. J. Angel, A. E. Finefrock, K. L. French, D. R. Hurst, A. R. Williams, M. E. Rampey, S. L. Studer-Martinez and C. F. Beam, “Preparation of N-Aryl-4-oxo-4H-1-benzothiopyran-2-acetamides from Trilithiated Acetoacetanilides and Lithiated Methyl Thiosalicylate,” Canadian Journal of Chemistry, Vol. 77, No. 1, 1999, pp. 94-97.
[11] K. L. French, A. J. Angel, A. R. Williams, D. R. Hurst and C. F. Beam, “A New Preparation of Substituted 4H-1-Benzothiopyran-4-Ones from C(a), N-benzoyl Hydrazones or C(a), n-Carboalkoxy Hydrazones and Methyl Thiosalicylate,” Journal of Heterocyclic Chemistry, Vol. 35, No. 1, 1998, pp. 45-48.
[12] C. E. Foster and P. R. Mackie, “Comprehensive Organic Functional Group Transformations II,” Elsevier Ltd, Oxford, 2005, p. 244.
[13] A. M. Marini, F. Da Settimo, S. Salerno, C. La Motta, F. Simorini, S. Taliani, D. Bertini, O. Gia and L. Dalla Via, “Synthesis and in Vitro Antiproliferative Activity of New Substituted Benzo[3′,2′:5,6]thiopyrano[4,3-d]pyrimidines,” Journal of Heterocyclic Chemistry, Vol. 45, No. 3, 2008, pp. 745-749. http://dx.doi.org/10.1002/jhet.5570450318
[14] A. S. Abbas, H. N. Hafez and A. B. A. El-Gazzar, “Synthesis, in Vitro Antimicrobial and in Vivo Antitumor Evaluation of Novel Pyrimidoquinolines and Its Nucleoside Derivatives,” European Journal of Medicinal Chemistry, Vol. 46, No. 1, 2011, pp. 21-30.
[15] H. N. Hafez, H. A. Hussein and A. B. A. El-Gazzar, “Synthesis of Substituted Thieno[2,3-d]pyramidine -2,4-dithiones and Their S-Glycoside Analogues as Potential Antiviral and Anti-Bacterial Agents,” European Journal of Medicinal Chemistry, Vol. 45, No. 9, 2010, pp. 4026-4034. http://dx.doi.org/10.1016/j.ejmech.2010.05.060
[16] H. N. Hafez and A. B. A. El-Gazzar, “Synthesis and Antitumor Activity of Substituted Triazolo-[4,3-a]pyrimidin-6-Sulfonamide with an Incorporated Thiazolidinone Moiety,” Bioorganic & Medicinal Chemistry Letters, Vol. 19, No. 15, 2009, pp. 4143-4147.
[17] A. B. A. El-Gazzar, H. N. Hafez and H. A. S. Abbas, “S-and C-Nucleosidoquinazoline as New Nucleoside Analogs with Potential Analgesic and Anti-Inflammatory Activity,” European Journal of Medicinal Chemistry, Vol. 44, No. 10, 2009, pp. 4249-4258.
[18] J. A. Halperin, A. Natarajan, Y. Guo, F. Harbinski, Y. H. Fan, H. Chen, L. Luus, J. Diercks, H. Aktas and M. Chorev, “Novel Arylsulfonamide-Oxindole Hybrid as an Anticancer Agent That Inhibits Translation Initiation,” Journal of Medicinal Chemistry, Vol. 47, No. 21, 2004, pp. 4979-4982. http://dx.doi.org/10.1021/jm0496234
[19] M. C. Alley, D. A. Scudiero, A. Monks, M. L. Hursey, M. J. Czerwinski, D. L. Fine, B. J. Abbot, J. G. Mayo, R. H. Shoemaker and M. R. Boyd, “Feasibility of Drug Screening with Panels of Human Tumor Cell Lines Using a Microculture Tetrazolium Assay,” Cancer Research, Vol. 48, No. 3, 1988, pp. 589-601.
[20] M. R. Grever, S. A. Schepartz and B. A. Chabner, “The National Cancer Institute: Cancer Drug Discovery and Development Program,” Oncology, Vol. 19, No. 6, 1992, pp. 622-638.
[21] M. R. Boyd and K. D. Paull, “Some Particles Consideration and Applications of the NCI in Vitro Anticancer Drug Discovery Screen,” Drug Development Research, Vol. 34, No. 2, 1995, pp. 91-109.
[22] A. Monks, D. Scudiero, P. Skehan, R. Shoemaker, K. Paull, D. Vistica, C. Hose, J. Langley, P. Cronise, A. Vaigro-Wolff, M. Gray-Goodrich, H. Campbell, J. Mayo and M. Boyd, “Feasibility of a High-Flux Anticancer Drug Screen Using a Diverse Panel of Cultured Human Tumor Cell Lines,” Journal of the National Cancer Institute, Vol. 83, No. 11, 1991, pp. 757-766.
[23] J. N. Weinstein, T. G. Myers, P. M. Connor, S. H. Friend A. J. Fornace Jr., K. W. Kohn, T. Fojo, S. E. Bates, L. V. Rubinstein, N. L. Anderson, J. K. Buolamwini, W. W. van Osdol, A. P. Monks, D. A. Scudiero, E. A. Sausville, D. W. Zaharevitz, B. Bunow, V. N. Viswanadhan, G. S. Johnson, R. E. Wittes and K. D. Paull, “An InformationIntensive Approach to the Molecular Pharmacology of Cancer,” Science, Vol. 275, No. 5298, 1997, pp. 343-349.
[24] K. Yoshimatsu, A. Yamaguchi, H. Yoshino, N. Koyanagi and K. Kitoh, “Mechanism of Action of E7010, an Orally Active Sulfonamide Antitumor Agent: Inhibition of Mitosis by Binding to the Colchicine Site of Tubulin,” Cancer Research, Vol. 57, No. 1, 1997, pp. 3208-3213.

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