Vargha László et al. (szerk.): Beszámoló a Gyógyszeripari Kutató Intézet 10 éves működéséről 1950-1959 (Budapest, 1969)

Dr. Vargha László et al.: Citosztatikus hatású cukorszármazékok

5. Diazoketones: 1-diazo-l-deoxy-glucoheptulose (XCIII), l,8-bis-diazo-2,7-dioxo-3,4,5,6 galactotetrahydroxy-octane (XCVI).

Besides the sugar derivatives we also prepared some hydroxyl-free analogues (XIV, XV, LXIX, LXX), chiefly for comparison of effectivity, further chloroethylamides of gluconic, glucosaccharic and mannosaccharic acide (LXII, XLIII, XLIV).

Among these types of compounds group 2. showed the best results with animal experiment as concerns toxicity, anti-tumoral and cytostatic effects. One member of this group, viz the D-mannitol derivative, has been registered under the trade name Degranol for use in treating haematological malignancies, such as lymphogranulomatosis, chronic lymphoid and myeloid leukaemia, and melanosarcoma. Of group 4. 1,6-dimesyl- D-mannitol (LXXIV) seems to affect distinctively myeloid elements of blood, and has, at the same time, minimal toxicity. Therefore, it is worth-while of trial for myeloid leukaemia.

A strong anti-tumour activity is proper to compound IX of group 1., whilst the members of group 3. and the hydroxyl-free analogues, in general, are for their high toxicity unsuited to practice. Among the diazoketones XCVI revealed a medium inhibitory effect.

Concerning structure-action relationship, it has been stated that the presence of hydroxyls in group 2. is essential for anti-tumour activity, since hydroxyl-free analogues (XIV, XV) proved ineffective. Besides, activity is influenced by the configuration the length of carbon-chain, and, at last, the sort of the halogens. Acid amides (XLII, XLIII, XLIV) were ineffective.