The cytotoxicity of 1-(phenylmethyl)-4,7,10-tris-[(4'methylphenyl) sulfonyl]-1,4,7,10-tetraazacyclododecane in human Tmolt3 T leukemic cells.
1-(phenylmethyl)-4,7,10-tris-[(4'methylphenyl)-sulfonyl]-1,4,7, 10-tetraazacyclododecane proved to possess potent in vivo antineoplastic and in vitro cytotoxicity in murine and human tissue cultured cells. In Tmolt3 leukemic cells 1-(phenylmethyl)-4,7,10-tris-[(4'methylphenyl)sulfonyl]-1,4,7, 10-tetraazacyclododecane inhibited the activities of the regulatory enzymes of the purine pathway leading to significant reductions in both RNA and DNA synthesis. Other sites of action of the compound which led to reductions of nucleic acid synthesis were suppression of nucleoside kinase and thymidylate synthetase activities and reductions in the d[NTP] pool levels. DNA fragmentation occurred which should be linked directly with cancer cell death.
Hall
I H
IH
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27759-7360, USA.
Elkins
A L
AL
Karthikeyan
S
S
Spielvogel
B F
BF
D000970:Antineoplastic Agents / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D053938:DNA Fragmentation / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006801:Humans; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000473:pathology; D012313:RNA / Q000096:biosynthesis; D013450:Sulfones / Q000494:pharmacology*
C105767:1-(phenylmethyl)-4,7,10-tris((4'-methylphenyl)sulfonyl)-1,4,7,10-tetraazacyclododecane; D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D013450:Sulfones; D012313:RNA; D004247:DNA