Twenty previously synthesized fused heterocyclic DNA-topoisomerase II (Topo 
II)-inhibiting compounds were investigated for their potential efficacy in 
various human cancer cell lines that were derived from different tumor entities. 
Moreover, different multidrug-resistant variants of these cancer cell lines with 
decreased Topo II expression were investigated. In parental, drug-sensitive 
cells merely the compounds BD3 and G35 showed efficacies, in terms of microM, 
which were similar to that of the classical Topo II inhibitor etoposide. On the 
other hand, most of the tested heterocyclic compounds were found more effective 
in drug-resistant cells than in the parental, drug-sensitive ones, and some of 
the compounds showed high antineoplastic efficacy in several drug-resistant cell 
models. Compounds BD13, BD14 and BD16 exhibited high antineoplastic activities 
against the drug-resistant sublines EPG85-257RNOV and EPG85-257RDB derived from 
gastric carcinoma, EPP85-181RNOV and EPP85-181RDB derived from pancreatic 
carcinoma, MCF-7/Adr derived from breast cancer, D79/86RNOV derived from 
fibrosarcoma, and MeWoETO1 derived from melanoma. Furthermore, compound D23 was 
found highly efficient in the multidrug-resistant variants HT-29RNOV and 
HT-29RDB derived from colon carcinoma, and compound D24 exhibited the highest 
antineoplastic activity among the tested compounds in the drug-resistant subline 
MDA-MB-231ROV derived from breast cancer. In conclusion, compounds BD 13, BD 14, 
BD 16, D 23 and D 24 may be useful for the treatment of different 
multidrug-resistant cancer cells with cross resistance against "classical" Topo 
II-targeting drugs.