A series of novel 5-H indolo[2,3-b]quinoline derivatives bearing (dialkylamino)alkyl chains at C-2 or C-9 position attached to indoloquinoline core via nitrogen, amide or ether bond were prepared and tested for ability to break multidrug resistance in cancer cells.

In our research we used three various human cancer cell lines and their drug-resistant sublines: human colon cancer (LoVo) and doxorubicin-resistant LoVo/DX (P-gp-dependent, MRP-, LRP-dependent multidrug resistance), uterine sarcoma (MES-SA) and MES-SA/DX5 (P-gp-dependent resistance to doxorubicin), human promyelocytic leukemia cell line (HL-60) and HL-60/MX2 (P-gp-independent and topoisomerase II-dependent resistance).

The results of our investigations showed that all these compounds were able to overcome the barrier of drug resistance. The compounds of this group had the highest activity against leukemia cell line. Only the compound ISS-22 did not show ability to overcome the barrier of drug resistance against human colon cancer and uterine sarcoma cell line. However, against leukemia cell line the ability to overcome this barrier, was similar to other compounds. The most effective derivatives of the all 5-H indoloquinolines tested were those which were connected with indoloquinoline core via ether bond.

RI^* was calculated according to the formula RI=(ID50 estimated against resistant cell line)/(ID50 estimated against non-resistant cell line); values range: 0<RI<2-indicate that the tested compound is able to overcome drug resistance; 2<RI<10 - defines the moderate ability of the compound to overcome drug resistance; RI>10 - defines no influence on the drug resistance phenomenon.

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