Cytotoxicity of 3,4-dihalogenated 2(5H)-furanones

Autor:	D. Kinchington, Harjit Singh, Simon Dunn, Washington Odur Ayuko, Eric Lattmann, Michael J. Tisdale
Rok vydání:	2004
Předmět:	Pharmacology Carbamate medicine.medical_treatment Pharmaceutical Science Epoxide Antineoplastic Agents Aziridine Chloride Mice chemistry.chemical_compound Ammonia 4-Butyrolactone chemistry Cell Line Tumor Lipophilicity medicine Animals Organic chemistry Furans Cytotoxicity IC50 medicine.drug
Zdroj:	Journal of Pharmacy and Pharmacology. 56:1163-1170
ISSN:	2042-7158 0022-3573
DOI:	10.1211/0022357044201
Popis:	Mucohalogen acids have been used for the preparation of a variety of 3,4-dihalogenated 2(5H)-furanones. In one synthetic step the carbamates 2a-c and the pseudoanhydrides 4a-e were prepared using isocyanates and acid anhydrides. A series of 5-alkoxylated 3,4-dichloro-2(5H)-furanones 5a-o have been synthesized with a wide range of lipophilicity, using the hydroxy-form of mucohalogen acids 1a and 1b. The 5-allyl-3,4-dichloro-2(5H)-furanone 5f was derived into the dihydro-isoxazol 6 and the oxirane 7. The methyl ester 5a was converted with ammonia into the tetramic acid chloride 11. The pseudo acid chloride 3 was reacted further into the bis aziridine 8. Reduction of the mucochloric acid 1a furnished the trichlorofuranone 3. The cytotoxicity of these simple and bis-cyclic butenolides have been evaluated in tissue culture on MAC13 and MAC16 cancer cell lines using the MTT cytotoxicity assay. The ester 5g, the acetate 4b and the carbamate 2b displayed a cytotoxicity in the low micromolar range. Further, an IC50 (50% inhibitory concentration) of 50 nM and 30 nM was determined for the epoxide 7 and the aziridine 8.
Databáze:	OpenAIRE
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