Synthesis, Antitumor and Antitubercular Evaluation of Certain New Xanthenone and Acridinone Analogs
| Autor: | Ashraf H. Abadi, Hussein I. El-Subbagh, Hamad A. Al-Khamees |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Antitubercular Agents
Antineoplastic Agents Cell Cycle Proteins Microbial Sensitivity Tests Pharmacology Chemical synthesis Mice chemistry.chemical_compound In vivo CDC2 Protein Kinase Drug Discovery Phosphoprotein Phosphatases Tumor Cells Cultured Animals Humans cdc25 Phosphatases Enzyme Inhibitors Cyclin-dependent kinase 1 Biological activity Mycobacterium tuberculosis Cell cycle In vitro Xanthenes chemistry Cell culture Acridines Drug Screening Assays Antitumor Growth inhibition |
| Zdroj: | Arzneimittelforschung. 49:259-266 |
| ISSN: | 1616-7066 0004-4172 |
| DOI: | 10.1055/s-0031-1300411 |
| Popis: | 6-Chloro-4-substituted methyl-4-xanthenones and 2,4-dichloro-1-substituted amino-9-(10 H)-acridinones were synthesized as tricyclic planar analogs and tested for their in vitro antitumor and antitubercular activity. The obtained derivatives were also evaluated for two biochemical, mechanism-based screens to explore their ability to inhibit the cell cycle control proteins cdc2 kinase and cdc25 phosphatase as molecular targets which may account for their antitumor activity. 4-(N1-Amidino)-sulphanilamidomethyl-6-chloro-9-xanthenone (10) proved to be the most active member of these derivatives exhibiting a broad spectrum antitumor potency against a wide range of human tumor cell lines with full panel median growth inhibition (GI50), total growth inhibition (TGI) and median lethal concentration (LC50) mean graph midpoint (MG-MID) values of 3.2, 12.7 and 21.8 mumol l-1, respectively. Meanwhile, compound 4-(N1-Acetyl)sulphanilamidomethyl-6-chloro-9-xanthenone (9) showed GI50, and TGI (MG-MID) values of 25.6 and 87.6 mumol l-1, respectively with a moderate selectivity for leukemia cell lines at the GI50 level. Compound 9 exhibited a weak in vivo growth inhibitory effect against many human tumor cells cultivated in hollow fibers and implanted into the intraperitoneal or subcutaneous physiologic compartments in mice. In addition, compounds 15, 20, 23-25 showed potential activity against mycobacterium strain H37Rv at 12.5 micrograms ml-1 concentration. The detailed synthess, spectroscopic and biological data are reported. |
| Databáze: | OpenAIRE |
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