In Vivo Antitumor Activity of Clitocine, an Exocyclic Amino Nucleoside Isolated from Lepista inversa

A biologically guided fractionation from Lepista inversa (Scop.: Fr.) led to the isolation of clitocine, an exocyclic amino nucleoside. This compound and two mixtures of β/α anomers (mixture A, 40:60 and mixture B, 80:20) were synthesized or isolated depending on the purification procedure. The β anomer and clitocine mixtures A and B showed similar cytotoxic activities with IC50 values ranging from 20.5 to 42 nM in murine cancer cell lines (3LL and L1210) and from 185 to 578 nM in human cancer cell lines (DU145, K‐562, MCF7, and U251). An in vivo study of mixture B was carried out on 3LL‐ and L1210‐tumor‐bearing mice. Clitocine solubilized in β‐hydroxypropylcyclodextrin and injected at concentrations of 0.5, 3, and 5 mg kg−1 did not significantly increase the survival rate and lifespan of 3LL‐tumor‐bearing mice. In contrast, clitocine showed antitumor activity on L1210‐tumor‐bearing mice with a significant increase in lifespan and a decrease in the development of ascites observed at 3 mg kg−1. The induction of apoptosis may be the basis of the antitumor activity of clitocine against L1210 as suggested by flow‐cytometry analysis of cells treated in vitro.