Potent antitumor N-mustard derivatives of 9-anilinoacridine, synthesis and antitumor evaluation

doi:10.1016/j.bmcl.2004.06.080

Bioorganic & Medicinal Chemistry Letters

Volume 14, Issue 18, 20 September 2004, Pages 4719-4722

https://doi.org/10.1016/j.bmcl.2004.06.080 Get rights and content

Abstract

A series of 9-anilinoacridine N-mustard derivatives, in which the alkylating N-mustard residue was linked to the C-3′ or C-4′ position of the anilino ring with an O-ethylene spacer, was synthesized and evaluated for cytotoxicity against human lymphoblastic leukemic cells (CCRF-CEM) in culture. The results showed that all of the new compounds exhibited potent cytotoxicity with IC₅₀ values ranging from 0.002 to 0.7 μM, which were as potent or significantly more potent than 3-(9-acridinylamino)-5-hydroxymethylaniline (AHMA). Compound 9 did not exhibit cross-resistance against both vinblastine-resistant (CCRF-CEM/VBL) and taxol-resistant (CCRF-CEM/taxol) cells. Additionally, compound 9 demonstrated potent antitumor effect in nude mice bearing human breast carcinoma MX-1 xenografts, resulting in complete tumor remission in two out of three mice at the maximal dose of 1–2 mg/kg (Q3D × 7) or 3 mg/kg (Q4D × 5) via intravenous injection.

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Acknowledgements

This work was supported by the National Science Council, Taiwan (Grant No. NSC90-2320-B-001-032). The NMR spectra of synthesized compounds were obtained at High-Field Biomacromolecular NMR Core Facility supported by the National Research Program for Genomic Medicine, Taiwan.

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Potent antitumor N-mustard derivatives of 9-anilinoacridine, synthesis and antitumor evaluation

Abstract

Graphical abstract

Section snippets

Acknowledgements

Prog. Nucl. Acids Res. Mol. Biol.

Bioorg. Med. Chem. Lett.

Cancer Res.

J. Med. Chem.

J. Med. Chem.

Anti-Cancer Drug Des.