全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用：99美元
投递稿件

查看量下载量

Synthesis and Antitumor Activity of Novel Thienopyrimidine Derivatives Containing Thiosemicarbazide Moiety

DOI: 10.4236/oalib.1102876, PP. 1-7

Subject Areas: Organic Chemistry, Medicinal Chemistry

Keywords: Synthesis, Thieno[2,3-d]Pyrimidine, Thiosemicarbazides, Anticancer Agents

Full-Text   Cite this paper   Add to My Lib

Abstract

The present study focused on synthesizing a series of novel derivatives of 4-aryl-1-[2-(3-benzyl-4-oxo(3H)-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-2-ylsulphanyl) acetyl] thiosemicarbazide 5a-d and evaluating their antitumor activity. The structure of the synthesized compounds has been elucidated on the basis of elemental analyses and spectroscopic methods (IR, 1H-NMR, 13C-NMR and MS). The in vitro cytotoxic activity of the synthesized derivatives was evaluated against two human cell lines: prostate cancer (PC-3) and colon cancer (HCT-116).

Cite this paper

Salib, S. B. , Khalil, O. M. , Kamel, M. M. and El-Dash, Y. (2016). Synthesis and Antitumor Activity of Novel Thienopyrimidine Derivatives Containing Thiosemicarbazide Moiety. Open Access Library Journal, 3, e2876. doi: http://dx.doi.org/10.4236/oalib.1102876.

References

[1]  Eckhardt, S. (2002) Recent Progress in the Development of Anticancer Agents. Current Medicinal Chemistry-Anti- Cancer Agents, 2, 419-439.
http://dx.doi.org/10.2174/1568011024606389
[2]  Abdel-Aziz, A.A.-M. (2007) Novel and Versatile Methodology for Synthesis of Cyclic Imides and Evaluation of Their Cytotoxic, DNA Binding, Apoptotic Inducing Activities and Molecular Modeling Study. European Journal of Medicinal Chemistry, 42, 614-626.
http://dx.doi.org/10.1016/j.ejmech.2006.12.003
[3]  Choo, H.-Y.P., Kim, M., Lee, S.K., Kim, S.W. and Chung, I.K. (2002) Solid-Phase Combinatorial Synthesis and Cytotoxicity of 3-Aryl-2,4-quinazolindiones. Bioorganic & Medicinal Chemistry, 10, 517-523.
http://dx.doi.org/10.1016/S0968-0896(01)00299-1
[4]  Zhou, B.B.S., Huang, H., Damelin, M., Geles, K.G., Grindley, J.C. and Dirks, P.B. (2009) Tumour-Initiating cells: Challenges and Opportunities for Anticancer Drug Discovery. Nature Reviews Drug Discovery, 8, 506-523.
http://dx.doi.org/10.1038/nrd2137
[5]  Liu, L.T., Yuan, T.T., Liu, H.H., Chen, S.F. and Wu, Y.T. (2007) Synthesis and Biological Evaluation of Substituted 6-Alkynyl-4-anilinoquinazoline Derivatives as Potent EGFR Inhibitors. Bioorganic & Medicinal Chemistry Letters, 17, 6373-6377.
http://dx.doi.org/10.1016/j.bmcl.2007.08.061
[6]  Wakeling, A.E., Guy, S.P., Woodburn, J.R., Ashton, S.E., Curry, B.J., Barker, A.J. and Gibson, K.H. (2002) ZD1839 (Iressa): An Orally Active Inhibitor of Epidermal Growth Factor Signaling with Potential for Cancer Therapy. Cancer Research, 62, 5749-5754.
[7]  Moyer, J.D., Barbacci, E.G., Iwata, K.K., Arnold, L., Boman, B., Cunningham, A., Diorio, C., Doty, J., Morin, M.J., Moyer, M.P., Neveu, M., Pollack, V.A., Pustilink, L.R., Reynolds, M.M., Salon, D., Theleman, A. and Miller, P. (1997) Induction of Apoptosis and Cell Cycle Arrest by CP-358,774, an Inhibitor of Epidermal Growth Factor Receptor Tyrosine Kinase. Cancer Research, 57, 4838-4848.
[8]  De Angelo, D.J., Stone, R.M., Heany, M.L., Nimer, S.D., Paquette, R.L., Klisovic, R.B., Caligiuri, M.A., Cooper, M.R., Leverf, J., Karol, M.D., Sheng, S., Holford, N., Curtin, P.T., Druker, B.J. and Heinrich, M.C. (2006) Phase 1 Clinical Results with Tandutinib (MLN518), a Novel FLT3 Antagonist, in Patients with Acute Myelogenous Leukemia or High-Risk Myelodysplastic Syndrome: Safety, Pharmacokinetics, and Pharmacodynamics. Blood, 108, 3674-3681.
http://dx.doi.org/10.1182/blood-2006-02-005702
[9]  Katada, J., Iijima, K., Muramatsu, M., Takami, M., Yasuda, E., Hayashi, M., Hattori, M. and Hayashi, Y. (1999) Cytotoxic Effects of NSL-1406, a New Thienopyrimidine Derivative, on Leukocytes and Osteoclasts. Bioorganic & Medicinal Chemistry Letters, 9, 797-802.
http://dx.doi.org/10.1016/S0960-894X(99)00088-8
[10]  Gangjee, A., Qiu, Y. and Kisliuk, R.L. (2004) Synthesis of Classical and Nonclassical 2-Amino-4-oxo-6-benzylthie- no[2,3-d]pyrimidines as Potential Thymidylate Synthase Inhibitors. Journal of Heterocyclic Chemistry, 41, 941-946.
http://dx.doi.org/10.1002/jhet.5570410613
[11]  Dai, R.L., Guo, Y., Frey, R.R., Ji, Z., Curtin, M.L., Ahmed, A.A., Albert, D.H., Arnold, L., Arries, S.S., Barlozzari, T., Bauch, J.L., Bouska, J.J., Bousquet, P.F., Cunha, G.A., Glaser, K.B., Guo, J., Li, J., Marcotte, P.A., Marsh, K.C., Moskey, M.D., Pease, L.J., Stewart, K.D., Stoll, V.S., Tapang, P., Wishart, N., Davidsen, S.K. and Michaelides, M.R. (2005) Thienopyrimidine Ureas as Novel and Potent Multitargeted Receptor Tyrosine Kinase Inhibitors. Journal of Medicinal Chemistry, 48, 6066-6083.
http://dx.doi.org/10.1021/jm050458h
[12]  Wang, Y.D., Johnson, S., Powell, D., McGinnis, J.P., Miranda, M. and Rabindran, S.K. (2005) Inhibition of Tumor Cell Proliferation by Thieno[2,3-d]pyrimidin-4(1H)-one-based Analogs. Bioorganic & Medicinal Chemistry Letters, 15, 3763-3766.
http://dx.doi.org/10.1016/j.bmcl.2005.05.127
[13]  Jennings, L.D., Kincaid, S.L., Wang, Y.D., Krishnamurthy, G., Beyer, C.F., McGinnis, J.P., Miranda, M., Discafani, C.M. and Rabindran, S.K. (2005) Parallel Synthesis and Biological Evaluation of 5,6,7,8-Tetrahydrobenzothieno[2,3- d]pyrimidin-4(3H)-one Cytotoxic Agents Selective for p21-Deficient Cells. Bioorganic & Medicinal Chemistry Letters, 15, 4731-4735.
http://dx.doi.org/10.1016/j.bmcl.2005.07.072
[14]  Nandi, A.K., Chaudhri, S., Mazumdah, S.K. and Ghosh, S. (1984) Effect of Chlorine Substitution on the Structure and Activity of 4-Phenylthiosemicarbazide: Crystal and Molecular Structure of 4-(4-Chlorophenyl) Thiosemicarbazide. Journal of the Chemical Society, Perkin Transactions 2, No. 11, 1729-1733.
http://dx.doi.org/10.1039/p29840001729
[15]  Ali, M.A., Chowdhary-I, D.A. and Uddin, M.N. (1984) Four- and Five-Coordinate Copper (II) Complexes Containing Mixed Ligands. Polyhedron, 3, 595-598.
http://dx.doi.org/10.1016/S0277-5387(00)88093-6
[16]  Scovill, J.P., Klayman, D.L. and Franchino, C.F. (1982) 2-Acetylpyridine Thiosemicarbazones. 4. Complexes with Transition Metals as Antimalarial and Antileukemic Agents. Journal of Medicinal Chemistry, 25, 1261-1264.
http://dx.doi.org/10.1021/jm00352a036
[17]  Gewald, K. (1965) Heterocyclen aus CH-aciden Nitrilen, VII. 2-Amino-thiophene aus α-Oxo-mercaptanen und Methylenaktiven Nitrilen. Chemische Berichte, 98, 3571-3577.
http://dx.doi.org/10.1002/cber.19650981120
[18]  Devani, M.B., Shishoo, C.J., Pathak, U.S., Parikh, S.H., Shah, G.F. and Padhya, A.C. (1976) Synthesis of 3-Substituted Thieno[2,3-d]pyrimidin-4(3H)-one-2-mercaptoacetic Acids and Their Ethyl Esters for Pharmacological Screening. Journal of Pharmaceutical Sciences, 65, 660-664.
http://dx.doi.org/10.1002/jps.2600650507
[19]  Skehan, P., Storeng, R., et al. (1990) New Colorimetric Cytotoxicity Assay for Anticancer-Drug Screening. Journal of National Cancer Institute, 82, 1107-1112.
http://dx.doi.org/10.1093/jnci/82.13.1107
[20]  Tacar, O., Sriamornsak, P. and Dass, C.R. (2013) Doxorubicin: An Update on Anticancer Molecular Action, Toxicity and Novel Drug Delivery Systems. Journal of Pharmacy and Pharmacology, 65, 157-170.
http://dx.doi.org/10.1111/j.2042-7158.2012.01567.x

Full-Text


comments powered by Disqus

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133

WeChat 1538708413




©2008-2020 OALib, Inc | Public user content licensed CC-BY 4.0 unless otherwise specified. OALib ISSN Online: 2333-9721 OALib ISSN Print: 2333-9705