Indenoisoquinoline has some advantages over camptothecin. First,
the DNA cleavage site of NSC314622 (4) is different from that of
camptothecin (1), so it is possible for different cancer resistance. Secondly,
the indoeritol-soluble Top1-DNA complexes of indenoisoquinoline are
more stable. Third, the indenoisoquinoline is chemically stable. Fourthly,
the indenoisoquinoline was less affected by the top1-resistant mutants of
R364H and N722S. Two indenoisoquinolines toxic Top1: indotecan (5),
indimitecan (6), were phase I clinical trials for cancer treatment and are
undergoing Phase II clinical trials.
Figure 1
In addition, research into hybrid compounds is gaining much interest
among researchers, recent studies have shown that hybridizations can
increase activity and some cases avoidance Drug resistance versus one
component.
Thus, the synthesis of new derivatives and cytotoxic activity assays
for the detection of antitoxin-active agents of Topoisomerase 1 is of great
scientific and practical significance. Therefore, we chose to study
“Synthesis and identification biological activity of some
indenoisoquinoline derivatives”.