Topoisomerase as target for antibacterial and anticancer drug discovery

Figures & data

Figure 1.  Classification of topoisomerases.

Figure 2.  Structures of antibiotics.

Figure 3.  Camptothecin (8).

Figure 4.  Structure of non-camptothecin drugs.

Table 1.  Eukaryotic and prokaryotic topoisomerases types and their function.

Eukaryotic Topoisomerases	Human I	Topoisomerases I	Relaxes negatively and positively supercoiled DNA
	Human II	Topoisomerases IIα	No supercoiling activity. Function unknown
	Human II	Topoisomerases IIβ	No supercoiling activity. Function unknown
Prokaryotic Topoisomerases	E. Coli I	Topoisomerases I	Relaxes only negatively supercoiled DNA
	E. Coli I	Topoisomerases III	Involved in chromosome stability and plasmid segregation
	E. Coli II	DNA Gyrase	Introduces negative supercoiling. Required for chromosome replication/segregation
	E. Coli II	Topoisomerases IV	No supercoiling activity. Required for chromosome segregation/cell division

Table 2.  Structure of CPT analogues.

Analogue	R1	R2	R3	R4
Topotecan (Hycamtin)	−H	CH2N(CH3)2	−OH	H
(CPT-11, Camptosar)	CH2CH3	H		H

Figure 5.  Structures of novel topoisomerases I inhibitor.

Figure 6.  Structure of ICRF-193 (bisdioxopiperazine) and HU-331.

Figure 7.  Structures of intercalating topo targeting drugs.

Figure 8.  Structure of non-intercalating targeting drug.

Figure 9.  2,4,6 trisubstitued pyridine moiety.

Figure 10.  Structures of tetracyclic moieties.

Table 3.  Structures of flavones.

Position Flavones	3	5	7	3′	4′	5′
Quercetin	OH	OH	OH	OH	OH	-
Kaempferol	OH	OH	OH	-	OH	-
Apigenin	H	OH	OH	H	OH	H
Fisetin	OH	H	OH	OH	OH	H

Figure 11.  Structure of glycosylated diphyllin derivative.

Figure 12.  Structures of nepalensinol-topo II inhibitor.

Figure 13.  Dual targeting topoisomerases inhibitor.