Synthesis and Cytotoxic Activity of Novel 9-[Hydroxy(Substitutedphenyl) Methyl]-2,2-Dimethyl-2,3,8,9-Tetrahydro-4H,10H-Pyrano [2,3-f ]Chromene-4,10-Diones

Document Type : Research Article

Authors

1 Iranian Research Institute of Plant Protection (IRIP), Tehran, I.R. IRAN

2 Department of Medicinal Chemistry, Faculty of Pharmacy, and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, I.R. IRAN

3 Department of Medicinal Chemistry, Faculty of Pharmacy, and Drug Design & Development Research Center, Tehran, Tehran University of Medical Sciences, I.R. IRAN

4 Institute of Biochemistry and Biophysics (IBB), University of Tehran, P.O. Box 13145-1384 Tehran, I.R. IRAN

5 Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran, Tehran University of Medical Sciences, I.R. IRAN

Abstract

Chromanone derivatives demonstrate remarkable cytotoxity against a varieties of cancer cell lines. Novel 9-[hydroxy(substitutedphenyl)methyl]-2,2-dimethyl-2,3,8,9- tetrahydro-4H,10H-pyrano[2,3-f]chromene-4,10-diones as Glyasperin analogues were synthesized in four steps from known 4-chromone 1. The key step was the preparation of chromane dione 5a by regioselective intramolecular cyclization reaction in 85% yield. Condensation of 5a with substituted aromatic aldehydes afforded corresponding alpha hydroxybenzyl analogues 6a-6e. The cytotoxic study of the synthesized compounds against breast cancer human cell line (T47D) showed moderate cytotoxic activities (IC50=16-40 μM) compared to the positive control drug vincristin (IC50=2.5 μM).

Keywords

Main Subjects


[1] Zhang H., Kasibhatla S., Kuemmerle J., Kemnitzer W., Ollis-Mason K., Qiu L., Crogan-Grundy C., Tseng B., Drewe J., Xiong Cai S., Discovery and Structure-Activity Relationship of 3-Aryl-5-aryl-1,2,4-oxadiazoles as a New Series of Apoptosis Inducers and Potential Anticancer Agents, J. Med. Chem., 48, p. 5215 (2005).
[2] Aliabadi A., Shamsa F., Ostad S.N., Emami S., Shafiee A., Davoodi J., Foroumadi A., Synthesis and Biological Evaluation of 2-Phenylthiazole-4-Carboxamide Derivatives as Anticancer Agents, Eur. J. Med. Chem., 45, p. 5384 (2010).
[3] Broxterman H.J., Georgopapadakou N.H., Anticancer Ttherapeutics: “Addictive” Targets, Multi-Targeted Drugs, New Drug Combinations, Drug Resist Updat., 8, p. 183 (2005).
[4] Satoh Y., Stanton J.L., Hutchison A.J., Libby A.H., Kowalski T.J., Lee W.H., White D.H., Kimble E.F., Substituted Chromenes as Potent, Orally Active 5-Lipoxygenase Inhibitors, J. Med. Chem., 36, p. 3580 (1993).
[5] Alizadeh B.H., Foroumadi A., Ardestani S.K., Poorrajab F., Shafiee A., Synthesis and Leishmanicidal Evaluation ofNovel4-Substituted-2,2-Dimethyl-7-(prop-2-ynyloxy)Chromenes, Turk. J. Chem. 33, p. 47 (2009).
[6] Alizadeh B.H., Ostad S.N., Foroumadi A., Amini R., Dowlatabadi M., Navidpour L., Shafiee A., Synthesis and Cytotoxic Activity of Novel Chromenes, Arkivoc, 13, p. 45 (2008).
[7] Alizadeh B.H., Foroumadi A., Ardestani S.K., Poorrajab F., Shafiee Leishmanicidal Evaluation of Novel Synthetic Chromenes, A., Arch. Pharm. Chem. Life Sci., 341, p. 787 (2008).
[8] Mahmoodi M., Aliabadi A., Emami S., Safavi M., Rajabalian S., Mohagheghi M.A., Khoshzaban A., Samzadeh-Kermani A., Lamei N., Shafiee A., Foroumadi A., Synthesis and in-Vitro Cytotoxicity of Poly-functionalized4- (2-Arylthiazol -4-yl) -4H-chromenes, Arch Pharm (Weinheim), 343, 7, 411 (2010).
[9] Alizadeh B.H., Foroumadi A., Emami S., Khoobi M., Panah F., Ardestan S.K., Shafiee A., Isochaihulactone Analogues: Synthesis and Anti-Proliferative Activity of Novel Dibenzylbutyrolactones, Eur. J. Med. Chem.,xxx ,1 (2010).
[10] Corey E.J., Useful Procedures For Oxidation of Alcohols Involving Pyridinium Dichromate id Aprotic Media, Tetrahedron. Lett., 5, p. 399 (1979).
[11] Bowden K.," Oxidation of Alcohols ", J. Chem. Soc., 39 (1946).
[12] Camps F., Coll J., Messeguer A., Pericas M.A., Ricart S., An Improved Procedure for the Preparation of 2,2-Dimethyl-4-Chromanones, Syn. Communn., 725 (1980).
[13] Jolivet C., Rivalle C., Bisagni E., Synthesis of Pyrano[2,3-h]Quinolines as Tricyclic Acronycine Analogues, Heterocycles, 43, p. 995 (1996).
[14] Koch K., General Preparation 4-Chromanones: Sythesis of a Potent Aldose Reductase Inhibitor, J. Org. Chem., 59, p. 1216 (1999).
[15] Tomioka K., Mizuguchi H., Koga K., Stereoselective Reactions. V. Design of the Asymmetric Synthesis of Lignan Lactones. Synthesis of optically Active Podorhizon and Deoxypodorhizon by 1, 3-Asymmetric Induction, Chem. Pharm. Bull., 30, p. 4304 (1982).
[16] Mosmann T., Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays, J. Immunol. Methods., 65, p. 55 (1983).
[17]  Saydam G., Aydin H.H., Sahin F., Selvi N., Oktem G., Terzioglu E., Buyukkececi F., Omay S.B., Involvement of Protein Phosphatase 2A in Interferon-α-2b-Induced Apoptosis in K562 Human Chronic Myelogenous Leukaemia Cells, Leuk Res., 27, p. 709 (2003).