Synthesis and cytotoxic evaluation of some 6-arylidene-2-(alpha-hydroxyamino-alpha-arylmethyl)cyclohexanone oximes and related compounds.
Reaction of 2,6-bis-(phenylmethylene)cyclohexanone (1) with a 4-molar excess of hydroxylamine hydrochloride and sodium acetate to produce the corresponding oxime 2 gave rise to 2-(alpha-hydroxyamino-alpha-phenylmethyl)-6-phenylmethylenecyclohexan one oxime (5a), whose structure was deduced from high-resolution proton nuclear magnetic resonance spectroscopy and confirmed by X-ray analysis. Compound 2 was eventually prepared from 1 with hydroxylamine per se and not with a mixture of hydroxylamine hydrochloride and sodium acetate. Ten analogues of 5a, namely 5b-5k, were prepared and evaluated for cytotoxicity. Six of the 11 compounds in series 5, as well as 1, showed activity in the 240-950 microM range against murine mammary EMT6 cells. Series 5 was also examined for cytotoxicity in an in vitro screen conducted by the National Cancer Institute with approximately 54 cell lines, and four compounds demonstrated selective toxicity toward various groups of tumors.
Dimmock
J R
JR
College of Pharmacy, University of Saskatchewan, Saskatoon, Canada.
Sidhu
K K
KK
Quail
J W
JW
Jia
Z
Z
Duffy
M J
MJ
Reid
R S
RS
Kirkpatrick
D L
DL
Zhu
L
L
Fletcher
S M
SM
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003512:Cyclohexanones / Q000138:chemical synthesis* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D010091:Oximes / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; D003512:Cyclohexanones; D010091:Oximes