Three simplified pyrazole analogs of the antitumor agents CC-1065 were synthesized. In in vitro assays against L1210 cell lines all derivs. showed a cytotoxicity in a pM range, values close to the natural target compd. (+)-CC-1065. In in vivo tests, against disseminate L1210 leukemia cells, synthesized compds. showed a good potency (O.D. 300 υg/Kg) but no activity. These observations further validate the effect of the hydrophilic and/or hydrophobic characteristics of the substituents present on the mols., confirming the relevance of this phenomena on in vivo activity. In fact in this case the increase of hydrophobic characteristics of the mols. produce the loss of activity, probably due to a worse bio-availability of the drugs in animals.
Synthesis, cytotoxicity and antitumor activity of some new simplified pyrazole analogs of the antitumor agent CC-1065. Effect of an hydrophobic group on antitumor activity
BARALDI, Pier Giovanni;CACCIARI, Barbara;ROMAGNOLI, Romeo;
1997
Abstract
Three simplified pyrazole analogs of the antitumor agents CC-1065 were synthesized. In in vitro assays against L1210 cell lines all derivs. showed a cytotoxicity in a pM range, values close to the natural target compd. (+)-CC-1065. In in vivo tests, against disseminate L1210 leukemia cells, synthesized compds. showed a good potency (O.D. 300 υg/Kg) but no activity. These observations further validate the effect of the hydrophilic and/or hydrophobic characteristics of the substituents present on the mols., confirming the relevance of this phenomena on in vivo activity. In fact in this case the increase of hydrophobic characteristics of the mols. produce the loss of activity, probably due to a worse bio-availability of the drugs in animals.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
