Topoisomerase II activity

The plant is known to produce norbisabolane diterpenes, including phyllanthusols A and B, which are both cytotoxic (36). From the bark, pentacyclic triterpenoids, phyl-lanthol, and olean-12en-3[3-ol (p-amyrin) have been isolated (37). Note lupane- and oleanane-type triterpenoids isolated from the bark of Phyllanthus flexuosus, such as olean-12-en-3 (3,15 a-diol, olean-12-en-3 [3,15 a,24-triol, lupeol, and betulin inhibited the enzymatic activity of topoisomerase II activity with IC50 values in the range of 10 to 39 p.M (38). 

Inhibition of topoisomerase II activity tn vitro f NT 47 Chen Eastmond... 

Isomarinone (1679), an isomer of the previously known marinone (7), was isolated from the same tropical sediment bacterium (1638). Another marine-derived bacterium related to the genus Streptomyces has yielded the novel azamerone (1680) (1639). The British Columbian medicinal plant Moneses uniflora contains the antibiotic 8-chlorochimaphilin (1681), which is more active than chimaphilin (1640). Sesame roots (Sesamum indicum) have yielded the red chlorinated naphthoquinone chlorosesamone (1682) (1641). Cultures of Streptomyces strain LL-A9227 produce chloroquinocin (1683), which has some antibacterial activity against Gram-positive bacteria (1642). The two xestoquinones 1684 and 1685 were characterized from the Philippino sponge Xestospongia sp., and display topoisomerase II activity (1643). 

Quercetin inhibits topoisomerase II activity. Similar to genistein, it enhances topoisomerase-II-dependent DNA cleavage complexes. It also inhibits topoisomerase-II-catalyzed ATP hydrolysis. Because quercetin is an intercalative compound, it may enhance DNA cleavage by a mechanism similar to that of doxorubicin. Quercetin also inhibits several PTKs, with IC50 values that are comparable to or lower than those of genistein. 

Arctigenin (38), (-)-tracheloside (189) and etoposide (VP-16-213, 65) showed a strong cyto-protective effect against human immunodeficiency virus type-l(HIV-l) in vitro, and efficiently inhibited both cellular topoisomerase II activity and the... 

Matsuo K, Kohno K, Takano H, Sato S, Kiue A, Kuwano M. Reduction of drug accumulation and DNA topoisomerase II activity in acquired teniposide-resistant human cancer KB cell lines. Cancer Res 1990 50 5819 5824. 

The topoisomerase II activity of the T. maritima DNA gyrase has been investigated by assessing the supercoiling activity of the purified enzyme. In order to... 

Colwill RW, Sheinin R (1983) ts A1S9 locus in mouse L cells may encode a novobiocin binding protein that is required for DNA topoisomerase II activity. Proc Natl Acad Sci USA 80 4644-4648... 

Goodell, J.R., Ougolkov, A.V., Hiasa, H., Kaur, H., Remmel, R., Billadeau, D.D. and Ferguson, D.M. 2008. Acridine-based agents with topoisomerase II activity inhibit pancreatic cancer cell proliferation and induce apoptosis. J. Med. Chem. 51(2) 179-182. 

Figure S Redrawn and modified model of topoisomerase 11 catalysis as proposed by Roca and Wang (159). Doxorubicin, daunorubicin, other 10-descarbomethoxy anthracyclines, and other topoisomerase 11 poisons" inhibit topoisomerase II activity by stabilization of the "cleavable com-ptex" (i.e., freezing the catalytic cycle between steps 3 and 4), which results in an accumulation of DNA strand breaks, and ultimately, DNA degradation. Aclarubicin and possibly other anchracy-dines possessing the 10-carbomethoxy moiety inhibit topoisomerase II by inhibiting reaction 1, namely, the complexaiion of DNA and the enzyme.

Doxorubicin and other anthracyclines, such as daunorubicin, are believed to exhibit their antineoplastic activity through inhibition of topoisomerase II activity. This appears to occur in the absence of significant metal binding by the anthracyclines. Doxorubicin can, however, bind with iron(III) and this results in the formation of a redox-active complex that may cause untoward effects (Myers et al. 1986). Doxorubicin-iron(III) complexes have been shown to oxidatively damage membranes and inactivate protein kinase C, but the biological signficance of this is not well understood (Hannun et al. 1989). 

Elenic acid (Figure 1) was isolated from an Indonesian sponge, an undescribed species of Plakinastrella. Its structure, a C22 fatty acid with a phenol terminus, is remarkably unspectacular. With only two functionalized and widely separated termini the compound can easily be manipulated synthetically for discovery of its active moiety. Its topoisomerase II activity, 0.1 pg/mL, compares favorably with currently used clinical agents, as e.g. doxorubicin or etoposide. ... 

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