Comparative toxicities of mimosine and some chemically related compounds to mouse bone marrow cells in liquid culture.
Mimosine, a plant amino acid which is toxic in mammals, was shown to be a potent inhibitor of incorporation of [3H]thymidine in mouse bone marrow cells in liquid culture (is greater than 70% inhibition at a concentration of 2 x 10(-4) M). To determine the parts of the molecule responsible for the inhibitory mechanism the effects of 13 chemically related compounds were examined in this system. The structural features necessary for inhibitory activity of the 4(1H)-pyridones were (1) the 3-hydroxyl-4-oxo function of the pyridone ring together with (2) an alpha-alanine or a 2-aminoethyl side chain. Compounds based on several other hydroxy heterocyclic functions were either weakly active or inactive. 3-Hydroxy-4(1H)-pyridone, the goitrogen to which mimosine is converted in ruminants, was only slightly inhibitory. These results are compared with published information on the effects of some of these compounds on other types of mammalian cells in vitro. The mouse bone marrow system in which inhibition of incorporation of [3H]thymidine is used as an index of cytotoxicity was shown to be sensitive and reproducible, and could be useful for structure-activity investigations of other cytotoxic compounds.
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D003864:Depression, Chemical; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008898:Mimosine / Q000633:toxicity; D011728:Pyridones / Q000633:toxicity*; D013936:Thymidine / Q000378:metabolism
D011728:Pyridones; D008898:Mimosine; D004247:DNA; D013936:Thymidine