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Synthesis, solvolytic stability and cytotoxicity of a modified derivative of CPzI, a pyrazole analog of the alkylation subunit of the antitumor agent CC-1065: effect of the nitrogen substitution on the functional reactivity

Baraldi, P.G.; Cacciari, B.; Guiotto, A.; Romagnoli, R.; Spalluto, G.; Zaid, A.N.; Capolongo, L.; Cozzi, P.; Geroni, C.; Mongelli, N.

Farmaco 52(12): 717-723

1997

ISSN/ISBN: 0014-827X
PMID: 9648275
Document Number: 480816
The synthesis and the comparative preliminary biological evaluation of a new pyrazole analog (16) of the CC-1065 alkylating unit (CPI) are described. This new derivative showed low cytotoxicity against L1210 murine leukemia (IC50 3064 nM) with respect to reference compound, but contrarily to literature data, was found to be more stable to solvolysis than the natural derivative (+/-)-N-Boc-CPI (pH 3, t1/2 = 212 h vs. 37 h). The results of such investigation showed that alkylation of the pyrazole nitrogen caused a loss of cytotoxic activity in vitro against tumor cells. This experimental observation allowed us to confirm the importance of free N-H for the anticellular activity.

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