Synthesis and anticancer activity of (R,S)-9-(2,3-dihydro-1,4-benzoxathiin-3-ylmethyl)-9H-purines.

A series of eleven 2- and 6-substituted (R,S)-9-(2,3-dihydro-1,4-benzoxathiin-3-ylmethyl)-9H-purine derivatives was obtained by applying a standard Mitsunobu protocol that led to a six-membered ring contraction from (R,S)-3,4-dihydro-2H-1,5-benzoxathiepin-3-ol via an episulfonium intermediate. The signal approximately delta=151 ppm, which corresponds to the C4' carbon atom, is unequivocal proof of the N9' regioisomer. The potential of the target molecules as anticancer agents is reflected in their activity against the MCF-7 cancer cell line. The most active compounds have IC(50) values of (6.18+/-1.70) and (8.97+/-0.83) microM. The results indicate that the anticancer activity for the most active compounds is correlated with their capacity to induce apoptosis.

Characterization of the antihypoxic activity of tisochromid.

The antihypoxic activity of tisochromid is compared with the well-known restituting effect of piracetam on posthypoxic dopamine release inhibition. In addition to a distinct restituting effect which accelerates the normalization of dopamine release highly, tisochromid exhibits obviously an antioxidative potency which is responsible for a greater effectiveness of the drug when given prehypoxically. Therefore, tisochromid acts simultaneously as a protective and a restituting drug.

[Antihypoxic effect of tisochromide (16-244) in comparison with piracetam]. / Untersuchungen zur antihypoxischen Wirksamkeit von Tisochromid (16-244) im Vergleich zu Piracetam.

The antihypoxic activity of Tisochromide (3-[4'-dimethylamino-4'-methylpentyl(2')-carbamoyl]-6,7-dimethoxy-1-thiaisochroman-1,1-dioxide), a substance of clinically antidepressant action, is studied on three hypoxia models and compared with that of the nootropic agent Piracetam: -- Tisochromide produces a dosis-dependent prolongation of the survival time of mice exposed to nitrogen hypoxia. -- The hypoxia-induced increase of lactate and pyruvate in the mouse brain is inhibited by this preparation. -- As to anoxia-induced electroencephalographic changes in the rat. Tisochromide increases the cerebral resistance against anoxia and shortens the isoelectric part of the encephalogram as well as the postanoxic phase of normalization.

[Operational evaluation studies in psychopharmacological research (presented with an example of a comparison between clomipramine and tisocromide)]. / Operationale Auswertungsverfahren in der psychopharmakologischen Forschung (dargestellt am Beispiel des Vergleichs Clomipramin und Tisocromid).

Departing from false interpretations of results obtained in psychopharmacological studies, the mathematical-statistical methods of the trend test after WILCOXON, of the WILCOXON comparative test for processes and of the HOTELLING-PABST test are presented and discussed on the basis of a computer programme. Using the example of the psychotropics clomipramine and tisocromide, differential-typological aspects have been recognised. These permit to draw conclusions for the optimisation of pharmacotherapy as well as reactions on the psychopharmacological development research. In the appraisal of the effectiveness of psychotropic substances a greater fundamental importance should be attached to operational procedures.