Toxicity, antitumour and haematological effects of 1,2-anhydro-6-bromogalactitol and d-mannitol: a comparison with the related dibromo- and dianhydro-derivatives.
1,2-Anhydro-6-bromo-6-deoxygalactitol (BrEpG) and its D-mannitol analogue (BrEpM) intermediary metabolites in the conversion of dibromodulcitol (DBD) and dibromomannitol (DBM) into dianhydrogalactitol (DAG) and dianhydromannitol (DAM) have been prepared. The three types of derivative of each hexitol have been compared in their toxicities towards mice, tumour inhibitory activities against the Walker carcinosarcoma and haematological effects in rats. The bromoepoxides showed intermediate potency in all tests. The galactitol derivatives were always more potent than their mannitol counterparts. The mannitol derivatives were selectively myelosuppressive, being twice as toxic towards granulocytes as towards lymphocytes. The lymphotoxic activity of DBM, in particular, relative to its other toxic effects was particularly mild. These differences have been ascribed principally to the more rapid reactivity of DAG compared with DAM towards target nucleophiles, modulated by the influence of the bromine substituent on the transport properties of the dibromo- and bromoepoxy-derivatives.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity; D002279:Carcinoma 256, Walker / Q000188:drug therapy*; D003961:Dianhydrogalactitol / Q000627:therapeutic use / Q000633:toxicity; D007928:Lethal Dose 50; D007970:Leukopenia / Q000139:chemically induced; D008353:Mannitol / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D051379:Mice; D008927:Mitobronitol / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D008936:Mitolactol / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats
D000970:Antineoplastic Agents; C010439:dianhydromannitol; D008353:Mannitol; D003961:Dianhydrogalactitol; D008927:Mitobronitol; C035725:1,2-anhydro-6-bromogalactitol; C035726:1,2-anhydro-6-bromomannitol; D008936:Mitolactol