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Biomedical subjects

S K Daley

Publications and source records attributed to S K Daley.

2 recordsLinked to original sources

Platinum complexes with anticancer potential and their evaluation by a colorimetric lambda prophage induction assay.

A simple biochemical phage induction assay (BIA) showed significant activity with 90% of the antitumor platinum compounds tested and lack of activity for all Pd(II) compounds and Pt(II) cationic complexes, compounds that are expected to be inactive. Structure-activity relationships for a large number of chemicals can be studied simultaneously by this simple, rapid, inexpensive and quantitative biochemical assay. Fifty-three platinum complexes were tested, including a number of ethylenediamines synthesized for this work. The magnitude of inducing activity varied over a 25-fold range; differences among analogs reflected structural differences in a chemically consistent manner. Seven platinum complexes showed greater activity than that of cis-diamminedichloroplatinum(II) (cisplatin, cis-DDP), while other compounds appeared to be substantially less toxic. The assay was predictive for most compounds with very high or very low activity in vivo against L1210. For compounds with intermediate levels of activity, no correlation between inducing and antitumor activity was observed.

Antineoplastic Agents

Direct quantitative analysis of indicine-N-oxide in cancer patient samples by gas chromatography using the internal standard heliotrine-N-oxide including a mass spectral comparison of their trimethylsilyl derivatives.

Indicine-N-oxide was analyzed quantitatively in biological samples using a direct partial purification method involving acetonitrite precipitation or methanol precipitation followed by ion exchange chromatography. Trimethylsilyl derivatization of the resultant provided either of two derivatives, depending on the reaction conditions used, both of which had good gas chromatographic qualities. Heliotrine-N-oxide was used as the internal standard for this work. Data are presented to show that this is a reliable and useful internal standard based on its behavior in the partial purification method and on the gas chromatographic characteristics of its two derivatives. In addition, both low and high resolution mass spectral data indicate that heliotrine-N-oxide produces two trimethylsilyl derivatives analogous to those produced by indicine-N-oxide under the same conditions. Application of this procedure to urine and blood samples from cancer patients in clinical trials indicates that over 95% of the drug is removed from the circulation and excreted in the urine over the course of 48 h.

Antineoplastic Agents, Phytogenic