Antitumour activity of suramin analogues in human tumour cell lines and primary cultures of tumour cells from patients

Suramin has shown promising antitumour activity against several tumour type s, both in vitro and in vivo, but the clinical utility of this compound is hampered by its unfavourable toxicity profile. In the present study, the se mi-automated fluorometric microculture cytotoxicity assay (FMCA) was employ ed for evaluation of the cytotoxicity of seven suramin analogues in vitro i n a panel of human tumour cell lines and in primary cultures of tumour cell s from patients. Like suramin, the analogues showed little sensitivity to r esistance mechanisms involving P-glycoprotein, topoisomerase II, multidrug resistance associated protein and glutathione-mediated drug resistance. In the cell line panel, NF067 and FCE 26644 showed activity comparable with su ramin. All analogues were less potent than suramin in patient cells except for FCE 26644. Correlation to suramin activity patterns in the cell line pa nel was highest for NF037 and low to moderate for the remaining analogues. In patient cells, high correlation coefficients were obtained for FCE 26644 , NF110, NF031 and NF037. The results indicate that the cytotoxic activity of suramin on patient tumour cells is shared by the analogues with FCE 2664 4 being the most active. The pharmacophore for cytotoxicity in patient cell s may be different from that observed in the cell lines. (C) 2000 Published by Elsevier Science Ltd. All rights reserved.