Potent antitumor N-mustard derivatives of 9-anilinoacridine, synthesis and antitumor evaluation.
作者： Valeriy A. Bacherikov , Ting-Chao Chou , Hua-Jin Dong , Ching-Huang Chen , Yi-Wen Lin
DOI: 10.1016/J.BMCL.2004.06.080
关键词:
摘要: Abstract A series of 9-anilinoacridine N-mustard derivatives, in which the alkylating residue was linked to C-3′ or C-4′ position anilino ring with an O-ethylene spacer, synthesized and evaluated for cytotoxicity against human lymphoblastic leukemic cells (CCRF-CEM) culture. The results showed that all new compounds exhibited potent IC 50 values ranging from 0.002 0.7 μM, were as significantly more than 3-(9-acridinylamino)-5-hydroxymethylaniline (AHMA). Compound 9 did not exhibit cross-resistance both vinblastine-resistant (CCRF-CEM/VBL) taxol-resistant (CCRF-CEM/taxol) cells. Additionally, compound demonstrated antitumor effect nude mice bearing breast carcinoma MX-1 xenografts, resulting complete tumor remission two out three at maximal dose 1–2 mg/kg (Q3D × 7) 3 mg/kg (Q4D × 5) via intravenous injection.
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sci-hub.se 参考文章(14)
B. Singer, The chemical effects of nucleic acid alkylation and their relation to mutagenesis and carcinogenesis. Progress in Nucleic Acid Research and Molecular Biology. ,vol. 15, pp. 219- 284 ,(1975) , 10.1016/S0079-6603(08)60121-X
Masao Koyama, Kiyobumi Takahashi, Ting Chao Chou, Zbigniew Darzynkiewicz, Jan Kapuscinski, T. Ross Kelly, Kyoichi A. Watanabe, Intercalating agents with covalent bond forming capability. A novel type of potential anticancer agents. 2. Derivatives of chrysophanol and emodin. Journal of Medicinal Chemistry. ,vol. 32, pp. 1594- 1599 ,(1989) , 10.1021/JM00127A032
Trudi A Gourdie, Kisione K Valu, G Lance Gravatt, Theodore J Boritzki, Bruce C Baguley, Laurence PG Wakelin, William R Wilson, Paul D Woodgate, William A Denny, None, DNA-directed alkylating agents. 1. Structure-activity relationships for acridine-linked aniline mustards: consequences of varying the reactivity of the mustard. Journal of Medicinal Chemistry. ,vol. 33, pp. 1177- 1186 ,(1990) , 10.1021/JM00166A015
S. J. Danishefsky, T.-C. Chou, O. A. O'Connor, W. P. Tong, Y. Guan, Z.-G. Zhang, S. J. Stachel, C. Lee, The synthesis, discovery, and development of a highly promising class of microtubule stabilization agents: Curative effects of desoxyepothilones B and F against human tumor xenografts in nude mice Proceedings of the National Academy of Sciences. ,vol. 98, pp. 8113- 8118 ,(2001) , 10.1073/PNAS.131153098
Paolo Cozzi, Italo Beria, Marina Caldarelli, Laura Capolongo, Cristina Geroni, Stefania Mazzini, Enzio Ragg, Phenyl sulfur mustard derivatives of distamycin A. Bioorganic & Medicinal Chemistry Letters. ,vol. 10, pp. 1653- 1656 ,(2000) , 10.1016/S0960-894X(00)00295-X
Tsann-Long Su, Ching-Huang Chen, Lin-Fei Huang, Chao-Hao Chen, Manas K. Basu, Xiu-Guo Zhang, Ting-Chao Chou, Synthesis and structure-activity relationships of potential anticancer agents: alkylcarbamates of 3-(9-acridinylamino)-5-hydroxymethylaniline. Journal of Medicinal Chemistry. ,vol. 42, pp. 4741- 4748 ,(1999) , 10.1021/JM9901226
P O'Dwyer, D Reilly, D D Von Hoff, E Patricia, D DeMaria, T Mooneyham, M Rocchetti, L V Vitek, I Poggesi, F Whaley, G R Weiss, A phase I and pharmacokinetic study of tallimustine [PNU 152241 (FCE 24517)] in patients with advanced cancer. Clinical Cancer Research. ,vol. 4, pp. 53- 59 ,(1998)
Pier Giovanni Baraldi, Romeo Romagnoli, Antonio Entrena Guadix, Maria Josè Pineda de las Infantas, Miguel Angel Gallo, Antonio Espinosa, Alberto Martinez, John P. Bingham, John A. Hartley, Design, synthesis, and biological activity of hybrid compounds between uramustine and DNA minor groove binder distamycin A. Journal of Medicinal Chemistry. ,vol. 45, pp. 3630- 3638 ,(2002) , 10.1021/JM011113B
Bo Nilsson, Johan Hansson, Rolf Lewensohn, Ulrik Ringborg, Formation and removal of DNA cross-links induced by melphalan and nitrogen mustard in relation to drug-induced cytotoxicity in human melanoma cells. Cancer Research. ,vol. 47, pp. 2631- 2637 ,(1987)
Tsann-Long, Development of DNA topoisomerase II-mediated anticancer agents, 3-(9-acridinylamino)-5-hydroxymethylanilines (AHMAs) and related compounds Current Medicinal Chemistry. ,vol. 9, pp. 1677- 1688 ,(2002) , 10.2174/0929867023369231