Synthesis of cytotoxic 6E-hydroximino-4-ene steroids: structure/activity studies.
In an effort to determine the pharmaceutical utility and the structural requirements for activity against various tumor cell lines, several 6E-hydroximino-4-ene steroids with different side chains and degrees of unsaturation on ring A were synthesized in our laboratory. Evaluation of the synthesized compounds for cytotoxicity against P-388, A-549, HT-29, and MEL-28 tumor cells revealed that some important structural features are required for activity. The presence of a cholesterol-type side chain, which appears to play a major role in determining the biological activity, the existence of a ketone functionality at C-3, and an elevated degree of oxidation on ring A all result in higher bioactivity than other structural motifs.
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Departamento de Química Fundamental, Facultad de Ciencias, Universidad de A Coruña, Campus da Zapateira, 15071 A Coruña, Spain.
Rodríguez
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J
Jiménez
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D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002783:Cholestenones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006898:Hydroxylamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D051379:Mice; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
C432701:2-hydroxy-6-hydroxyiminocholesta-1,4-dien-3-one; D000970:Antineoplastic Agents; D002783:Cholestenones; D006898:Hydroxylamines; D013256:Steroids