Karel Vereš

Biological activity of hormonally active and non-active androgen derivatives

Androgen derivatives appeared to have different biological activities in vivo and in vitro. Testosterone-17-isobutyrate given in three doses of 50 or 200 microgram increased significantly the weight of seminal vesicles and reduced thymus weight in castrated males, whereas testosterone-17-hemisuccinate, testosterone-D-beta-glucoside and testosterone-3-(O-carboxymethyl)-oxime had no such effects. Similarly, ten 1-mg doses of testosterone-17-isobutyrate, unlike testosterone-17-hemisuccinate, resulted in a marked reduction of thymus weight in non-castrated males and in a significant inhibitory effect on the activity of spermatogenesis. On the other hand, all three androgen derivatives, which had appeared inactive in vivo, had similar effects in vitro (as had active testosterone) as demonstrated by inhibition of Concanavalin A-induced lymphocyte activation expressed by 14C thymidine incorporation and inhibition of cell agglutination. These results seem to suggest that as for the regulation of androgen-dependent organs and functions (such as the size of seminal vesicles, activity of spermatogenesis, thymus size), hormonally active androgens are also involved in certain immunosuppressive effects in vivo. On the other hand, in vitro immunological effects are produced by both hormonally active and non-active androgen derivatives as well as by other steroid hormones, the common denominator being the steroid structure.

A Simple Method of Preparation of Labelled Peptides Possessing Antibiotic Properties

Preparation of derivatives of peptide antibiotics polymyxin B and colistin- substituted on free amino groups by aminoacyl residues is described. The first procedure is based on the condensation of the antibiotic with active ester of a suitably protected amino acid. The second one makes use of Woodward’s reagent by condensation of the antibiotic with a protected amino acid. The following compounds were prepared: glycyl-14C-polymyxin B and glutaminyl-polymyxin B and glycylcolistin, also under conditions suitable for a radioactive synthesis. All the preparations preserve a substantial part of the biological activity comparable with polymyxin B and colistin.