more water-soluble. For example, is a derivate called CKD-602, which is a potent topoisomerase I inhibitor and successfully overcomes the poor water solubility and toxicity seen with CPT. Considerably greater activity can be achieved by putting electron-withdrawing groups like amino, nitro, bromo or chloro at position 9 and 10 and hydroxyl group at position 10 or 11. But these compounds are relatively insoluble in aqueous solutions, which causes difficulty in administrations. Methoxy group at both position 10 and 11 simultaneously leads to inactivity. Hexacyclic CPT analogues Hexacyclic CPT analogues have shown great potency. For example, methylenedioxy or ethylenedioxy group connected between 10 and 11 form a 5 or 6 membered ring which leads to more water-soluble derivates and increased potency. Researches have shown that ethylenedioxy analogues are less potent than methylenedioxy. The reason is the unfavorable steric interactions of ethylenedioxy analogues with the enzyme. Adding amino or chloro group at 9th position or chloromethyl group at 7th position to these 10, 11-methylenedioxy or ethylenedioxy analogues results in compounds with even greater cytotoxicity but weaker solubility in water. To yield 10, 11-methylenedioxy or ethylenedioxy analogues with good water solubility a good way is to introduce a water solubilising substituent at position 7. Lurtotecan meets those requirements; it’s a 10, 11-ethylenedioxy analogue with a 4-methylpiperazino-methylene at position 7 and has shown a great potency in clinical researches. A ring can also be formed between position 7 and 9, like position 10 and 11. That gives new opportunities to make water-soluble derivatives [5]. These hexacyclic CPT become more active when electron-withdrawing groups are put in position 11 and methyl or amino groups at 10. Exatecan is an example of hexacyclic CPT that has a 6 membered ring over position 7 and 9, and is 10-methyl, 11-fluoro substituted [4]. It is water-soluble and more potent than topotecan. C- and D-ring modification The C- and D-rings have an essential role in the antitumor activity. Replacement in any position results in much less potent compound than parent compound in other cytotoxicity assay. E-ring modifications The E-ring doesn’t allow many structural changes without losing CPT activity because it is necessary for binding to the active site of TOP I. One possible replacement is changing the hydroxyl group to Cl, F or Br because their polarizability is sufficient to stabilize the enzyme-complex. Another possible modification is to insert a methylene between hydroxyl and lactone on the E-ring yielding