Putative intermediates of cardenolide biosynthesis, namely progesterone, pregnenolone, 5 beta-pregnane-3,20-dione or 5 beta-pregnan-3 beta-ol-20-one, were administered to light- or dark-grown shoot cultures of Digitalis lanata. The unsaturated compounds were reduced to their respective 5 alpha-pregnanes, 5 beta-pregnane-3,20-dione was reduced to 5 beta-pregnan-3 alpha-ol-20-one and 5 beta-pregnan-3 beta-ol-20-one was isomerized to the respective 3 alpha-pregnane. Suspension cultures of Digitalis lanata, on the other hand, accumulated both the 3 alpha- and the 3 beta-isomer of 5 beta-pregnan-3-ol-20-one when incubated in the presence of 5 beta-pregnane-3,20-dione. When 5 beta-pregnan-3 alpha-ol-20-one was administered the cultured cells accumulated large amounts of the 3 beta-isomer together with small amounts of 5 beta-pregnane-3,20-dione, which may be regarded as an intermediate during the isomerization reaction. Cell-free, buffered extracts from light-grown shoots were shown to reduce 5 beta-pregnane-3,20-dione almost exclusively to 5 beta-pregnan-3 alpha-ol-20-one when 0.05 M MgCl2 were present in the incubation mixture. Under these conditions the formation of 5 beta-pregnan-3 beta-ol-20-one was inhibited. The enzyme activity could be recovered from membrane-free supernatants. Optimum enzyme activity occurred at pH 7.0 and 42 degrees C. The energy of activation was 56.2 kJ/mol and the enzyme reaction was found to be NADPH-dependent. SH reagents were essential for enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗

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Studies on drug resistance. V. Combination chemotherapy with cytosine arabinoside (NSC-63878) plus 6-thioguanine (NSC-752) in cytosine arabinoside-sensitive and -resistant P815 mouse neoplasms.

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Phase I trial of vinzolidine.

Vinzolidine is a new, orally active, semisynthetic vinca alkaloid which shows broad anti-tumor activity against murine tumor test systems. This phase I study established a 1 day every 2 week schedule of 35 mg/m2 in good-risk patients and of 30 mg/m2 in poor-risk patients. Maximal tolerated dose was 45 mg/m2 with severe neutropenia, syndrome of inappropriate antidiuretic hormone, and paralytic ileus. Significant antitumor responses were seen in two patients with lymphoma and in one with squamous cell cancer of the lung.

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