부산대학교 도서관

The three stereoisomers of the noncyclam compound 1(1(R,R), 1(S,S), and the mesoform 1(S,R)) and their corresponding tetrahydrochlorides 11wereprepared from (S)- and (R)-2-methylpiperidine.We have evaluated their inhibitory activity on the CXC chemokine receptortype 4 (CXCR4), toxicity properties, and assessment of their effecton glioma initiating cells (GICs) in comparison with the prototypecompound AMD3100. The IC50values determined on human recombinant(CHO) cells showed very similar inhibitory activities albeit a lower KBfor AMD3100, with the 1(R,R) isomer being second in potency. All the compounds showedlow cardiac toxicity but, contrary to AMD3100, gave maximum nonlethaldoses of around 2.0 mg/kg. The CXCR4 inhibitors had an effect on thestate of differentiation of GICs, decreasing the percentage of CD44cells in glioblastoma multiform neurospheres in vitro. Moreover, theseCXCR4 inhibitors blocked the capacity of cells to initiate orthotopictumors in immunocompromised mice. [ABSTRACT FROM AUTHOR]