D-19575 is a glucose derivative of ifosfamide mustard with a broad spectrum of antitumor activity in animal models. In comparison with ifosfamide, D-19575 is less toxic and is better tolerated by tumor-bearing animals, achieving a better therapeutic efficacy. D-19575 is directly cytotoxic in vitro--in contrast to ifosfamide--and it is possible to modulate this cytotoxicity by inhibition of transmembrane glucose transporters. Correspondingly, renal reabsorption of filtered D-19575 could be blocked by pre- and cotreatment with phlorizin, resulting in a higher urinary excretion of the unchanged drug. The toxicity to white blood cells, colony-forming units (CFU-C), and spleen-cell colony-forming units (CFU-S) is considerably lower for D-19575 as compared with ifosfamide. In conclusion, D-19575 is a new alkylating cytotoxic agent with increased antitumor selectivity, probably caused by an active transmembrane transport mechanism.
A series of low molecular compounds from Chinese herbal medicines which have proved to be, in some cases, highly effective especially in tumor therapy, is listed here (part II will deal with high molecular compounds, to be published in the next issue). In contrast to synthetic agents used in cancer chemotherapy, these natural compounds have relatively low toxicities. Many of the clinical studies referred to in this paper have been carried out on Asians. Because genetic factors influence enzyme levels, sometimes leading to striking differences in metabolism and pharmacokinetics of drugs, results obtained in clinical studies carried out in China are not 100 % transferable to the European population. The mechanisms of action of these compounds are manifold, consisting of reactions with DNA bases, intercalation in DNA, inhibition of topoisomerases, inhibition of protein kinases, induction of apoptosis etc. Some of the compounds have interesting structural features, that may be used as lead structures for the development of further antitumor agents.
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