DERIVATIVES OF 2-BENZYLIDENECYCLOHEXANONE AS POTENTIAL ANTINEOPLASTIC AGENTS
The aim of this research was to prepare some substituted 2-benzylidenecyclohexyl isothiocyanates, which would be screened against L-1210 lymphoid leukemia and the KB tumor. The first step in the synthesis involved the preparation of substituted (E)-2- benzylidenecyclohexanones, which are α,ß-unsaturated ketones, a class of compounds known to have alkylating properties. Only the substituted (E,E)-2,6-bis-(dichlorobenzylidene)cyclohexanones were isolated in the syntheses designed to yield (E)-2-(dichlorobenzylidene)cyclo-hexanones. All benzylidene derivatives were submitted for screening. The unsubstituted compound, (E)-2-benzylidenecyclohexanone, has a high level of activity against the KB tumor in vitro, and a low level of toxicity in mice. Ultraviolet irradiation resulted in isomerization of the substituted (E)-2-benzylidenecyclohexanones to the Z isomers. (Z)-2- Benzylidenecyclohexanone was isolated from the ultraviolet irradiation of the E isomer. Ultraviolet spectroscopy and the Braude equation were employed to study the degree of coplanarity of the conjugated system for some of the benzylidene derivatives. The mass spectra of the substituted (E)-2-benzylidenecyclo-hexanones and the substituted (E,E)-2,6-bis-benzylidenecyclohexanones were examined in detail. One of the major fragmentation pathways involved an intramolecular attack by the carbonyl oxygen on the ortho position of the aromatic ring, resulting in the formation of a benzopyrylium ion.
Doctor of Philosophy (Ph.D.)
Pharmacy and Nutrition