The synthesis, characterization, inhibitory activity against topoisomerase I, and biological evaluation of a series of 14 camptothecin derivatives of polypyrrolecarboxamide (lexitropsin) conjugates of two structural classes: (A) camptothecin-NHCO-lexitropsin 44-51 and (B) camptothecin-CONH-lexitropsin 38-43 are described. All 16 compounds tested, 14 conjugates plus two functionalized camptothecin controls, inhibit topoisomerase I in the concentration range 1.12-16.6 microM that divide into three distinct categories based on activity. The most active enzyme inhibitors belong to structure class A with either cationic dimethylaminium or neutral amide end groups. Generally class B conjugates are less effective in inhibiting topoisomerase I. Cytotoxic potencies of the drugs was tested against four representative human tumor cell lines: SKOV3, SKLVB, HT29, and KB. All 16 drugs gave measurable IC50 values against the KB cell line and fell into two categories with IC50 values of 0.049-0.66 microM (largely structure class B) and 1.0-48 microM (largely class A). Thus the class B conjugates, while less potent against the enzyme, contain two of the most potent drugs, 38 and 39, against KB cell lines. In contrast, in the case of the cell lines SKOV3 and HT29 there was a general correlation between the better topoisomerase inhibitors and their cell cytotoxicities.