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New Green Synthesis and Antineoplastic Activity of Bis (3-Arylimidazolidinyl-1) Methanes

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DOI: 10.4236/ojmc.2013.34014    4,759 Downloads   7,113 Views  

ABSTRACT

A new green synthesis and anti-tumor activity of the series of bis (3-arylimidazolidinyl-1) methanes 1 - 6 are described.
The compounds were synthesized from the corresponding N-arylethylenediamine and trioxane as sources of formaldehyde
and the reactions were performed in heterogeneous phase catalyzed by an acidic ion-exchange resin (Amberlyst
15). The compounds were tested with the Sulforhodamine B assay according to the protocol of the National Cancer Institute
for several cell lines. The results were expressed as percentage inhibition of growth cell in comparison with the
full growth of the cells without treatment. Cytotoxicity on normal cells using the Annexing-PI staining and flow cytometry
has been evaluated. The parent compound, bis(3-phenylimidazolidinyl-1)methane 1 and the monohalogenated
derivatives 4-chlorophenyl 3 and 3-bromophenyl 5 showed antineoplastic activity, 60%, 82% and 89% inhibition
growth cell respectively on the human colon cell line (HCT116). The 4-tolyl derivative 6 presented inhibitory activity (73%
inhibition of growth cell) on human lung adenocarcinoma cell line (A549) and 62% on human mammary cell line MCF-7.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

M. Caterina, I. Perillo, X. Villalonga, N. Amiano, C. Payés, M. Sanchez and A. Salerno, "New Green Synthesis and Antineoplastic Activity of Bis (3-Arylimidazolidinyl-1) Methanes," Open Journal of Medicinal Chemistry, Vol. 3 No. 4, 2013, pp. 121-127. doi: 10.4236/ojmc.2013.34014.

References

[1] [1] J. B. Gibbs, “Mechanism-Based Target Identification and Drug Discovery in Cancer Research,” Science, Vol. 287, No. 5466, 2000, pp. 1969-1973. http://dx.doi.org/10.1126/science.287.5460.1969
[2] C. Unger, “New Therapeutic Approaches in Cancer Treatment,” Drugs of the Future, Vol. 22, No. 12, 1997, pp. 1337-1345.
[3] P. Heffeter, M. A. Jacupec, W. Orner, S. Wild, N. G. Keyserlingk, L. Elbling, H. Zorbas, A. Korynevska, S. Knasmuller, H. Sutterluty, M. Micksche, B. K. Keppler and W. Berger, “Anticancer Activity of the Lanthanum Compound [Tris(1,10-phenanthroline) lanthanum(III)] tri thiocyanate (KP772; FFC24),” Biochemical Pharmacology, Vol. 71, No. 4, 2006, pp. 426-440. http://dx.doi.org/10.1016/j.bcp.2005.11.009
[4] J. Mann, A. Baron, Y. Opoku-Boahen, E. Johansson, G. Parkinson, L. R. Kelland and S. Neidle, “A New Class of Symmetric Bis-Benzimidazole-Based DNA Minor Groove Binding Agents,” Journal of Medicinal Chemistry, Vol. 44, No. 2, 2001, pp. 138-144. http://dx.doi.org/10.1021/jm000297b
[5] A. Seaton, C. Higgins, J. Mann, A. Baron, C. Bailly, S. Neidle and H. van den Berg, “Mechanistic and Anti-Proliferative Studies of Two Novel, Biologically Active Bis-Benzimidazoles,” European Journal of Cancer, Vol. 39, No. 17, 2003, pp. 2548-2555. http://dx.doi.org/10.1016/S0959-8049(03)00621-X
[6] Y.-H. Yang, M.-S. Cheng, Q.-H. Wang, H. Nie, N. Liao, J. Wang and H. Chen, “Design, Synthesis, and Anti-Tumor Evaluation of Novel Symmetrical Bis-Benzimida-zole,” European Journal of Medicinal Chemistry, Vol. 44, No. 17, 2009, pp. 1808-1812. http://dx.doi.org/10.1016/j.ejmech.2008.07.021
[7] H. A. Johnson and N. R. Thomas, “Polyhydroxylate-dazepanes as New Motifs for DNA Minor Groove Binding Agents,” Bioorganic & Medicinal Chemistry Letters, Vol. 12, No. 2, 2002, pp. 237-241. http://dx.doi.org/10.1016/S0960-894X(01)00719-3
[8] E. Rajanarendar, M. N. Reddy, S. R. Krishna, K. G. Reddy, Y. N. Reddy and M. V. Rajam, “Design, Synthesis, in Vitroantimicrobial And Anticancer Activity Of Novel Methylenebis-Isoxazolo[4,5-B]Azepines Derivatives,” European Journal of Medicinal Chemistry, Vol. 50, 2012, pp. 344-349. http://dx.doi.org/10.1016/j.ejmech.2012.02.013
[9] L. W. Deady, J. Desneves, A. J. Kaye, G. J. Finlay, B. C. Baguley and W. A. Denny, “Synthesis and Antitumor Activity of Some Indeno[1,2-b]Quinolone-Based Biscarboxamides,” Bioorganic & Medicinal Chemistry, Vol. 8, No. 5, 2000, pp. 977-984. http://dx.doi.org/10.1016/S0968-0896(00)00039-0
[10] R. Sánchez-Martín, J. M. Campos, A. Conejo-García, O. Cruz-López, M. Bánez-Coronel, A. Rodríguez-González, M. A. Gallo, J. C. Lacal and A. Espinosa, “Symmetrical Bis-Quinolinium Compounds: New Human Choline Kinase Inhibitors with Antiproliferative Activity against the HT-29 Cell Line,” European Journal of Medicinal Chemistry, Vol. 48, No. 9, 2005, pp. 3354-3363.
[11] S. Safe, S. Papineni and S. Chintharlapalli, “Cancer Chemotherapy with Indole-3-Carbinol, Bis(3’-Indolyl)-Methane and Synthetic Analogs,” Cancer Letters, Vol. 269, No. 2, 2008, pp. 326-338. http://dx.doi.org/10.1016/j.canlet.2008.04.021
[12] S. D. Cho, S. Chintharlapalli, M. Abdelrahim, S. Papineni, S. Liu, J. Guo, P. Lei, A. Abudayyeh and S. Safe, “5,5'-Dibromo-Bis(3'-Indolyl)Methane Induces Krüppel-Like Factor 4 and p21 in Colon Cancer Cells,” Molecular Cancer Therapeutics, Vol. 7, No. 7, 2008, pp. 2109-2120. http://dx.doi.org/10.1158/1535-7163.MCT-07-2311
[13] D. Bigg, S. Auvin, C. Lanco and G. Prevost, “Imidazolidine-2,4-Dione Derivatives and Use Thereof as a Medicament,” WO2010119194, 2010.
[14] G. Prevost, S. Auvin, C. Lanco, A. Liberatore and O. Lavergne, “Imidazolidine-2,4-Dione Derivatives, and Use Thereof as a Cancer Drugs,” EP 2 419 410, 2013.
[15] P. Y. Johnson and D. J. Kerkman, “The Chemistry of Hindered Systems. II. The Acyloin Reaction—An Approach to Regiospecifically Hydroxylated Tetramethy-lazacycloheptane Systems,” The Journal of Organic Chemistry, Vol. 41, No. 10, 1976, pp. 1768-1773. http://dx.doi.org/10.1021/jo00872a023
[16] P. Calabresi and J. Darnowski, “Use of Taurolidine to Treat Tumors,” US 6,429, 224, 2002.
[17] P. Calabresi, F. A. Goulette and J. W. Darnowski, “Taurolidine: Cytotoxic and Mechanistic Evaluation as a Novel Antineoplastic Agent,” Cancer Research, Vol. 61, No. 18, 2001, pp. 6816-6821.
[18] I. Perillo, E. Repetto, M. C. Caterina, R. Massa, G. Gut- kind and A. Salerno, “Synthesis, Spectroscopic and Bio- logical Properties of Bis(3-Arylimidazolidinyl-1)Methanes. A Novel Family of Antimicrobial Agents,” European Journal of Medicinal Chemistry, Vol. 40, No. 8, 2005, pp. 811-815. http://dx.doi.org/10.1016/j.ejmech.2005.03.010
[19] V. Sharma and M. S. Y. Khan, “Synthesis of Novel Tet- rahydroimidazole Derivatives and Studies for Their Bio- logical Properties,” European Journal of Medicinal Che- mistry, Vol. 36, No. 6, 2001, pp. 651-658. http://dx.doi.org/10.1016/S0223-5234(01)01256-9
[20] W. E. Craig and J. O. Van Hook, “Heterocyclic Ami- noalkil Imidazolidines and Hexahidropyrimidines,” US 2,675, 381, 1954.
[21] J. O. Van Hook and W. E. Craig, “N,N’-Bis(Aminoalkil) Derivatives of Imidazolines and Hexahidropyrimidines,” US 2,675, 387, 1954.
[22] M. C. Caterina, I. A. Perillo, L. Boiani, H. Pezaroglo, H. Cerecetto, M. Gonzalez and A. Salerno, “Imidazolidines as New Anti-Trypanosoma Cruzi Agents: Biological Evaluation and Structure-Activity Relationships,” Bioor- ganic & Medicinal Chemistry, Vol. 16, No. 5, 2008, pp. 2226-2234.
[23] M. C. Caterina, M. V. Corona, I. A. Perillo, A. Salerno, D. Benítez, H. Cerecetto and M. González, “Síntesis y Eva- luación in Vitro Frente a T. Cruzi de 1-Acil-3-Arilimi- dazolidinas,” 3er Workshop Argentino de Química Me- dicinal, Argentina, 2008, p. 47.
[24] G. S. de Carvalho, P. A. Machado, D. T. S. de Paula, E. S. Coimbra and A. D. da Silva, “Synthesis, Cytotoxicity, and Antileishmanial Activity of N,N'-Disubstitutede- thylenediamine and Imidazolidine Derivatives,” The Sci- entific World Journal, Vol. 10, 2010, pp. 1723-1728. http://dx.doi.org/10.1100/tsw.2010.176
[25] E. von Angerer, G. Kranzfelder, A. K. Taneja and H. Sch?nenberger, “N,N'-Dialkyl Bis(Dichorophenyl) Ethyl- enediamines and Imidazolidines: Relationship between Structure and Estradiol Receptor Affinity,” Journal of Medicinal Chemistry, Vol. 23, No. 12, 1980, pp. 1347- 1350. http://dx.doi.org/10.1021/jm00186a012
[26] E. von Angerer, G. Egginger, G. Kranzfelder, H. Bernhaus- er and H. Sch?nemberger, “N,N'-Dialkyl-1, 2-Bis(Hydro- xyphenyl) Ethylenediamines and N,N'-Dialkyl-4,5-Bis(4-Hy- droxyphenyl)Imidazolidines: Synthesis and Evaluation of Their Mammary Tumor Inhibitingactivity,” Journal of Medicinal Chemistry, Vol. 25, No. 7, 1982, pp. 832-837. http://dx.doi.org/10.1021/jm00349a013
[27] H. A. Nieper, “New Carcinostatic Compounds against Hela Cells,” ArztlForsch, Vol. 20, 1966, pp. 18-23.
[28] K. Sztanke, S. Fidecka, E. Kedzierska, Z. Karczmarzyk, K. Pihlaja and D. Matosiuk, “Antinociceptive Activity of New Imidazolidine Carbonyl Derivatives. Part 4. Synthe- sis and Pharmacological Activity of 8-Aryl-3,4-Dioxo- 2H,8H-6,7-Dihydroimidazo[2,1-c] [1,2,4]Triazines,” Euro- pean Journal of Medicinal Chemistry, Vol. 40, No. 2, 2005, pp. 127-134. http://dx.doi.org/10.1016/j.ejmech.2004.09.020
[29] P. Skehan, R. Storeng, D. Scudiero, A. Monks, J. Mc-Mahon, D. Vistica, J. T. Warren, H. Bokesch, S. Kenney and M. R. Boyd, “New Colorimetric Cytotoxicity Assay for Anticancer-Drug Screening,” Journal of the National Cancer Institute, Vol. 82, No. 13, 1990, pp. 1107-1112. http://dx.doi.org/10.1093/jnci/82.13.1107
[30] M. R. Grever, S. A. Schepartz and B. A. Chabner, “The National Cancer Institute: Cancer Drug Discovery and Development Program,” Seminars in Oncology, Vol. 19, No. 6, 1992, pp. 622-638.
[31] R. H. Shoemaker, “The NCI60 Human Tumour Cell Line Anticancer Drug Screen,” Nature Reviews Cancer, Vol. 6, No. 10, 2006, pp. 813-823. http://dx.doi.org/10.1038/nrc1951
[32] J. S. Driscoll, “The Preclinical New Drug Research,” Cancer Treatment. Reports, Vol. 68, No. 1, 1984, pp. 63- 67.
[33] I. Perillo, M. C. Caterina, J. Lopez and A. Salerno, “Syn- thesis of Substituted 1H-4,5-Dihydroimazolium Salt by Dehydrogenation of Imidazolidines,” Synthesis, No. 6, 2004, pp. 851-856.
[34] Y.-H. Liu, Q.-S. Liu and Z.-H. Zhang, “Amberlyst-15 as a New Andreusable Catalyst for Regioselective Ring- Opening Reactions of Epoxides to Alcoxy Alcohols,” Journal of Molecular Catalysis A: Chemical, Vol. 296, No. 1, 2008, pp. 42-46.
[35] L. D. Sasiambarrena, A. S. Cánepa and R. D. Bravo, “Synthesis of 1,2,4,5-Tetrahydro-3,2-Benzothiazepine 3,3-Dioxides Using Amberlyst-15,” Synthetic Communications, Vol. 41, No. 2, 2010, pp. 200-205. http://dx.doi.org/10.1080/00397910903533983
[36] R. Pal, T. Sarka and S. Khasnobis, “Amberlyst-15 in Organic Synthesis,” Arkivoc, Vol. 2012, No. 1, 2012, pp. 570-609. http://dx.doi.org/10.3998/ark.5550190.0013.114
[37] K. Singh, S. Sharma and A. Sharma, “Unique Versatility of Amberlyst 15. An Acid and Solvent-Free Paradigm towards Synthesis of Bis(Heterocyclyl)Methane Derivatives,” Journal of Molecular Catalysis A: Chemical, Vol. 347, No. 1, 2011, pp. 34-37. http://dx.doi.org/10.1016/j.molcata.2011.07.007

  
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