Synthesis of the acridone alkaloids glyfoline and congeners. Structure-activity relationship studies of cytotoxic acridones Journal Article
| Authors: | Su, T. L.; Köhler, B.; Chou, T. C.; Chun, M. W.; Watanabe, K. A. |
| Article Title: | Synthesis of the acridone alkaloids glyfoline and congeners. Structure-activity relationship studies of cytotoxic acridones |
| Abstract: | Glyfoline (4,1,6-dihydroxy-10-methyl-2,3,4,5-tetramethoxyacridin-9-one) and its congeners were synthesized for evaluation of their cytotoxicity. A detailed structure-activity relationships (SAR) of these acridone derivatives were also studied. To study the SAR of glyfoline analogues, substituent(s) at C-1 and C-6 and at the heterocyclic nitrogen of glyfoline nucleus were modified. Nitro- and amino-substituted glyfoline analogues were also synthesized to study the effects of substituent(s) (electron-withdrawing vs electron-donating) on their cytotoxicity. These compounds were synthesized via the Ullmann condensation of anthranilic acids with iodobenzenes or 2-chlorobenzoic acids with aniline derivatives. The SAR studies showed that 1-hydroxy-9-acridonee were more active than their 1-OMe derivatives against cell growth of human leukemic HL-60 cells in culture. Replacement of NMe of glyfoline with NH or N(CH 2 ) 2 NEt 2 resulted in either total loss or dramatic reduction of cytotoxicity. Glyfoline congeners with nitro function at the A-ring were inactive, while compounds with amino substituent were shown to be cytotoxic in vitro. © 1992, American Chemical Society. All rights reserved. |
| Keywords: | unclassified drug; human cell; drug activity; antineoplastic agents; cell survival; amino acid substitution; cytotoxicity; drug screening assays, antitumor; tumor cells, cultured; drug synthesis; structure activity relation; structure-activity relationship; acridines; leukemia cell line; growth inhibition; alkaloid; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; glyfoline; acridone derivative |
| Journal Title: | Journal of Medicinal Chemistry |
| Volume: | 35 |
| Issue: | 14 |
| ISSN: | 0022-2623 |
| Publisher: | American Chemical Society |
| Date Published: | 1992-07-01 |
| Start Page: | 2703 |
| End Page: | 2710 |
| Language: | English |
| DOI: | 10.1021/jm00092a022 |
| PUBMED: | 1635067 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Source: Scopus |
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