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Sulfuric Acid Catalyzed Preparation of Alkyl and Alkenyl Camptothecin Ester Derivatives and Antitumor Activity against Human Xenografts Grown in Nude Mice

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DOI: 10.4236/ojmc.2012.21002    3,347 Downloads   7,112 Views   Citations

ABSTRACT

Camptothecin-20-propinate (CZ48) and other camptothecin ester derivatives were prepared by the esterification reac-tions of camptothecin or 9-nitrocamptothecin with the corresponding acylating agents such as organic acid anhydride or chloride with concentrate sulfuric acid as the catalyst. The sulfuric acid-catalyzed reactions gave high yields of camptothecin ester products.Among the 11 compounds prepared by this method, camptothecin-20-O-propionate, camptothecin-20-O-crotonate, and 9-nitrocamptothecin-20-O-propionate showed good anticancer activity against various types of human tumors grown as xenografts in nude mice. The methodology developed for the preparation of camptothecin esters in this article can be applied to a wide scope of other ester derivatives.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Z. Cao, A. Kozielski, D. Vardeman and B. Giovanella, "Sulfuric Acid Catalyzed Preparation of Alkyl and Alkenyl Camptothecin Ester Derivatives and Antitumor Activity against Human Xenografts Grown in Nude Mice," Open Journal of Medicinal Chemistry, Vol. 2 No. 1, 2012, pp. 10-14. doi: 10.4236/ojmc.2012.21002.

References

[1] M. Wall, M. Wani, C. Cook, K. Palmer, A. McPhail and G. Sim, “Plant Antitumor Agents. I. The Isolation and Structure of Camptothecin, a Novel Alkaloidal Leukemia and Tumor Inhibitor from Camptotheca acuminata,” Journal of the American Chemical Society, Vol. 88, No. 16,1966, pp. 3888-3890. doi:10.1021/ja00968a057
[2] J. Gottlieb, A. Guarino, J. Call, V. Oliverio and J. Block, “Preliminary Pharmacologic and Clinical Evaluation of Camptothecin Sodium (NSC-100880),” Cancer Chemotherapy Reports: Part 1, Vol. 54, No. 6, 1970, pp. 461-470.
[3] J. Gottlieb and J. Luce, “Treatment of Malignant Melanoma with Camptothecin (NSC-100880),” Cancer Chemotherapy Reports, Vol. 56, No. 1, 1972, pp. 103-105.
[4] F. Muggia, P. Creaven, H. Hansen, M. Cohen and O. Selawry, “Phase I Clinical Trial of Weekly and Daily Treatment with Camptothecin (NSC-100880): Correlation with Preclinical Studies,” Cancer Chemotherapy Reports, Vol. 56, No. 4, 1972, pp. 515-521.
[5] C. Moertel, A. Schutt, R. Reitemeier and R. Hahn, “Phase II Study of Camptothecin (NSC-100880) in the Treatment of Advanced Gastrointestinal Cancer,” Cancer Chemotherapy Reports, Vol. 56, No. 1, 1972, pp. 95-101.
[6] M. Wani, P. Ronman, L. Lindley and M. Wall, “Plant Antitumor Agents. 18. Synthesis and Biological Activity of Camptothecin Analogs,” Journal of Medicinal Chemistry, Vol. 23, No. 5, 1980, pp. 554-560. doi:10.1021/jm00179a016
[7] T. Burke, “Chemistry of the Camptothecins in the Bloodstream: Drug Stabilization and Optimization of Activity in the Camptothecins—From Discovery to Patients,” Annals of the New York Academy of Sciences, Vol. 903, 1993, pp. 29-31.
[8] Z. Cao, N. Harris, A. Kozielski, D. Vardeman, J. Stehlin and B. Giovanella, “Alkyl Esters of Camptothecin and 9-Nitrocamptothecin: Synthesis, in Vitro Pharmacokinetics, Toxicity, and Antitumor Activity,” Journal of Medicinal Chemistry, Vol. 41, No. 1, 1998, pp. 31-37. doi:10.1021/jm9607562
[9] Z. Cao, J. Mendoza, A. DeJesus and B. Giovanella, “Synthesis and Antitumor Activity of Alkenyl Camptothecin Esters,” Acta Pharmacologica Sinica, Vol. 26, No. 2, 2005, pp. 235-241. doi:10.1111/j.1745-7254.2005.00031.x
[10] B. Neises and W. Steglich, “Simple Method for the Esterification of Carboxylic Acids,” Angewandte Chemie International Edition, Vol. 17, No. 7, 1978, pp. 522-524. doi:10.1002/anie.197805221
[11] A. Hassner and V. Alexanian, “Direct Room Temperature Esterification of Carboxylic Acids,” Tetrahedron Letters, Vol. 19, No. 46, 1978, pp. 4475-4478 doi:10.1016/S0040-4039(01)95256-6
[12] F. Ziegler and G. Berger, “A Mild Method for the Esterification of Fatty Acids,” Synthetic Communications, Vol. 9, No. 6, 1979, pp. 539-543. doi:10.1080/00397917908060958
[13] Z. Cao, J. Mendoza, A. DeJusus, D. Vardeman and B. Giovanella, “Synthesis and Antitumor Activity of Aromatic Camptothecin Esters,” International Journal of Molecular Medicine, Vol. 21, No. 4, 2008, pp. 477-487.
[14] Z. Cao, P. Pantazis, J. Mendoza, J. Early, A. Kozielski, N. Harris and B. Giovanella, “Structure-Activity Relationship of Alkyl 9-Nitrocamptothecin Esters,” Acta Pharmacologica Sinica, Vol. 24, No. 2, 2003, pp. 109-119.
[15] Z. Cao, P. Pantazis, J. Mendoza, J. Early, A. Kozielski, N. Harris, D. Vardeman, J. Liehr, J. Stehlin and B. Giovanella, “Structure-Activity Relationship of Alkyl Camptothecin Esters,” Annals of the New York Academy of Sciences, Vol. 922, 2000, pp. 122-135. doi:10.1111/j.1749-6632.2000.tb07031.x
[16] Z. Cao, A. Kozielski, X. Liu, Y. Wang, D. Vardeman and B. Giovaniella, “Crystalline Camptothecin-20(S)-Opropionate Hydrate: A Novel Anticancer Agent with Strong Activity against 19 Human Tumor Xenograts,” Cancer Research, Vol. 69, No. 11, 2009, pp. 4742-4749. doi:10.1158/0008-5472.CAN-08-4452
[17] Z. Cao, J. Mendoza, A. Kozielski, X. Liu, A. DeJesus, Y. Wang, C. Zhan, D. Vardeman and B. Giovanella, “Anticancer Activity of New Haloalkyl Camptothecin Esters against Human Cancer Cell Lines and Human Tumor Xenografts Grown in Nude Mice,” Submission.
[18] Z. Cao, K. Armstrong, M. Shaw, E. Petry and N. Harris, “Nitration of Camptothecin with Various Inorganic Nitrate Salts in Concentrated Sulfuric Acid: A New Preparation of Anticancer Drug 9-Nitrocamptothecin,” Synthesis, Vol. 1998, No. 12, 1998, pp. 1724-1730. doi:10.1055/s-1998-2207

  
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