Potent antitumor N-mustard derivatives of 9-anilinoacridine, synthesis and antitumor evaluation Journal Article
| Authors: | Bacherikov, V. A.; Chou, T. C.; Dong, H. J.; Chen, C. H.; Lin, Y. W.; Tsai, T. J.; Su, T. L. |
| Article Title: | Potent antitumor N-mustard derivatives of 9-anilinoacridine, synthesis and antitumor evaluation |
| 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 IC 50 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. © 2004 Elsevier Ltd. All rights reserved. |
| Keywords: | controlled study; unclassified drug; human cell; drug activity; nonhuman; antineoplastic agents; paclitaxel; chemotherapy; antineoplastic agent; mouse; animals; mice; animal experiment; antineoplastic activity; cytotoxicity; drug potency; drug screening; dose-response relationship, drug; drug resistance, neoplasm; tumor cells, cultured; xenograft model antitumor assays; drug design; drug synthesis; structure-activity relationship; breast neoplasms; vinblastine; mus musculus; cancer resistance; cell culture; mice, nude; cancer cell; breast carcinoma; 3 (9 acridinylamino) 5 hydroxymethylaniline; 9 anilinoacridine derivative; lymphatic leukemia; amsacrine; alkylating agents; ic 50; synthesis; acridines; injections, intravenous; nitrogen mustard compounds; aniline derivative; antitumor compounds; humans; human; article |
| Journal Title: | Bioorganic & Medicinal Chemistry Letters |
| Volume: | 14 |
| Issue: | 18 |
| ISSN: | 0960-894X |
| Publisher: | Pergamon-Elsevier Science Ltd |
| Date Published: | 2004-09-20 |
| Start Page: | 4719 |
| End Page: | 4722 |
| Language: | English |
| DOI: | 10.1016/j.bmcl.2004.06.080 |
| PROVIDER: | scopus |
| PUBMED: | 15324894 |
| DOI/URL: | |
| Notes: | Bioorg. Med. Chem. Lett. -- Cited By (since 1996):16 -- Export Date: 16 June 2014 -- CODEN: BMCLE -- Source: Scopus |
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