Synthesis and Cytotoxic Evaluation of Substituted Sulfonyl-N-hydroxyguanidine Derivatives as Potential Antitumor Agents
| Autor: | Chin-Fen Lee, Yen-Chywan Liaw, Shun-Li Wang, Yu-Ling Leu, Pei-Chie Tsou, Ji-Wang Chern, Ruwen Jou, Shaw-Man Hsu, Hua-Mei Lin |
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| Rok vydání: | 1997 |
| Předmět: |
Models
Molecular Magnetic Resonance Spectroscopy Cell Survival Stereochemistry Transplantation Heterologous Melanoma Experimental Molecular Conformation Antineoplastic Agents Calorimetry Crystallography X-Ray Guanidines Chemical synthesis KB Cells Mice Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Tumor Cells Cultured Animals Humans Cytotoxic T cell Moiety Cytotoxicity Sulfonyl chemistry.chemical_classification Mice Inbred C3H Sulfonamides Molecular Structure Chemistry Aromaticity In vitro Molecular Medicine Drug Screening Assays Antitumor Lead compound |
| Zdroj: | Journal of Medicinal Chemistry. 40:2276-2286 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm9607818 |
| Popis: | A series of sulfonyl-N-hydroxyguanidine derivatives was designed and synthesized for cytotoxic evaluation as potential anticancer agents on the basis of the lead compound LY-181984. Replacement of the ureido moiety of the lead compound with hydroxyguanidine provided a stable cytotoxic agent. The conformation of sulfonyl-N-hydroxyguanidine derivatives, such as N-(4-chlorophenyl)-N'-[(benzo[2,1,3]thiadiazol-4-yl)sulfonyl]-N"- hydroxyguanidine (4g), investigated utilizing HMBC NMR, theoretical calculations, and X-ray crystallography, indicated stacking of the two aromatic rings. The derivatives were evaluated for in vitro cytoxicity against five human tumor cell lines, including HepG2, TSGH 8302, COLO 205, KB, and MOLT-4. The cytotoxic activities of the derived compounds against the human tumor cell lines were equal to or greater than that of the lead compound. N-(4-Chlorophenyl)-N'-[[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl]- N"- hydroxyguanidine (4n) and N-(4-chlorophenyl)-N'-[[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl] sulfonyl]-N"-hydroxyguanidine (4o) exhibited the greatest growth inhibition of solid tumor cell lines. Compound 4o was found to possess antitumor activity against murine K1735/M2 melanoma xenografts. |
| Databáze: | OpenAIRE |
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