Tetra-acridine derivatives

A series of tetra-acridine derivatives 61 were examined (Scheme 21), among those acridines with H9 (61a), N9 (61b), and C19 (61c) groups, as dual inhibitors of topoisomerase II and the human proteasome (2007 MI1863). 

The anthraquinone derivative (2) represents the first example from 1997, with numerous others following in rapid succession, including the dibenzo-phenanthroline derivatives and tri-substituted acridines (3), which were reported to inhibit telomerase action in tumour cell lines with IC50 values of up to 28 and 60 nM, respectively. The tri-substituted acridines (3) were developed from the simple acridine (4) on the basis of structure-based design principles to maximise the quadruplex binding affinity. Thus, inhibition of telomerase by these compounds appears to be correlated to selective stabilisation of the human DNA quadruplex structure. Tetra-(A-methyl-4-pyridyl)-porphyrins... 

Several reports of pyrimidine-based anticancer agents were published in 2013. George and his collaborators reported the synthesis of novel tetra-hydrobenzo[4,5]thieno[2,3-d] pyridimidine derivatives and explored their antitumor and antibacterial activities (Figure 3) (13EJM195). Compounds 101 and 102 were found to be very active against the bacterial species Staphylococcus aureus (G" "), Pseudomonas aeruginosa (G ), Bacillus subtilis (G ), and Escherichia coli (G ). Furthermore, 9-methyl-A/-substi-tuted acridine-3,6-diamino derivative 103 was shown to be active solely... 

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