When one tries to evaluate molecules with topoisomerase
II activity using the criterion of sales, it is extremely difficult
because of the fact that all of the anthracyclines were discovered to exhibit this particular mechanism of action well
after the initial examples were approved for clinical use.
However the influence of such a mechanism can be seen by
inspection of the number of agents that are either totally
synthetic (predominately quinolone derivatives) or based
upon/are natural products that are in phase I to phase III
trials with this mechanism. Currently over 50 topoisomerase
II inhibitors are listed in Integrity. Of the 17 that have already
launched, 6 are either natural products or modifications
thereof. Of those in clinical trials, 16 are natural products or
based upon an NP skeleton, including such well-known
structures as tafluposide (podophyllotoxin; 3; Scheme 1) in
phase I and sabarubicin (doxorubicin; 70; Scheme 15) and
becatecarin (staurosporine; 69; Scheme 15) in phase II