SYNTHESIS, CYTOTOXICITY AND ANTITUMOR-ACTIVITY OF SOME NEW SIMPLIFIEDPYRAZOLE ANALOGS OF THE ANTITUMOR AGENT CC-1065 - EFFECT OF AN HYDROPHOBIC GROUP, ON ANTITUMOR-ACTIVITY

Three simplified pyrazole analogs (7-9) of the antitumor agents CC-106 5, were synthesized. In in vitro assays, against L1210 cell, lines all derivatives showed a cytotoxicity in a pM range, values close to the natural target compound (+)-CC-1065. In in vivo tests, against dissemi nate L1210 leukemia cells, synthesized compounds showed a good potency (O.D. 300 mu g/Kg) but no activity. These observations further valida te the effect of the hydrophilic and/or hydrophobic characteristics of the substituents present on the molecules, confirming the relevance o f this phenomena on in vivo activity. In fact in this case the increas e of hydrophobic characteristics of the molecules produce the loss of activity, probably due to a worse bioavailability of the drugs in anim als.