Synthesis and preliminary cytotoxicity of nitrogen mustard derivatives of distamycin A.
Distamycin and nitrogen mustard conjugates, in which the nitrogen mustard unit was coupled to the C-terminus of the pyrrole, were synthesized. The switching of the nitrogen mustard unit from the N-terminus to the C-terminus did not compromise the compound's cytotoxicity. Compound 3, bearing three pyrrole units, was highly toxic to human K562 leukemia cells in vitro with an IC(50) value of 0.03 microM. Addition of a trans double bond to the molecule had little effects on cytotoxicity.
Wang
Yuqiang
Y
Panorama Research, Inc., 2462 Wyandotte Street, Mountain View, CA 94043, USA. yuqiangwang@worldnet.att.net
Wright
Susan C
SC
Larrick
James W
JW
D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D004214:Distamycins / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D009588:Nitrogen Mustard Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D018906:Antineoplastic Agents, Alkylating; D004273:DNA, Neoplasm; D004214:Distamycins; D009588:Nitrogen Mustard Compounds; C030000:stallimycin