Cell Division Inhibitors

Cell Division Inhibitors. The most common mode of action of soil-appHed herbicides is growth inhibition, primarily through dkect or indkect interference with cell division (163). Such growth inhibitory activity is the basis for most pre- or post-emergent herbicides intended to control germinating weed seeds. In germinating seeds, cell division occurs in the meristems of the root and the shoot. Meristematic cells go through a cycle... 

Several /i-solenoid domains appear to promote the oligomerization of multidomain proteins. There are at least three types of /i-solenoid association. First, oligomers (dimers or trimers) are formed by lateral interaction of the solenoids. For example, the C-terminal domain of the bacterial cell division inhibitor MinC is a short right-handed T-type solenoid with an apolar lateral face that mediates homodimerization (Cordell et al., 2001). Trimers of several bacterial transferases are formed by lateral, in-register, interaction of left-handed T-type /1-solenoids (Fig. 5). Second, dimers may form via interactions of the open terminal coils of /1-solenoids as in the dimeric structure of iron transporter stabilizer SufD (Badger et al., 2005). Finally, dimerization may be mediated by swapping of /1-strands of the terminal coils, as in the CAP (Dodatko et al., 2004) (Fig. S). 

Cordell, S. C., Anderson, R. E., and Lowe, J. (2001). Crystal structure of the bacterial cell division inhibitor MinC. EMBO J. 20, 2454—2461. 

FIGURE 7.1 Characterization of cell division inhibitor PC190723. (A) Chemical structure of PC190723. (B) In vivo efficacy of PC190723 in a murine model of infection. Mice were injected intraperitoneally (IP) with a lethal inoculum of S. aureus ATCC 19636 at time 0. One hour after infection the animals received 3 mg/kg (uneven dashed line), 10 mg/kg (dotted line), or 30 mg/kg (dark line) of PC190723 negative control (vehicle only, dashed black line) or 3 mg/kg of the vancomycin control antibiotic (thick dark line) by subcutaneous (SC, top) or intravenous (IV, bottom) administration. Mortality was recorded daily for 7 days. (Source From Haydon, DJ. et al. 2008. Science 321, 1673, 2008. Reprinted with permission from AAAS.)... 

Cell division inhibitor. Primary target site may be F fatty acid metabolism... 

The final mitosis stage involves separation of two sets of chromosomes via microtubules that are filamentous polymers of tubulin monomers. Compounds that interfere with tubulin polymerization such as the plant-derived compounds colchicine, taxol, vinblastine and vincristine are cell division inhibitors (Table 9.6). The cytokinesis of the daughter cells requires equal division of cytoplasm and an actin-myosin-based contractile ring provides the force to make this separation. Accordingly, compounds such as cytochalasin B that interfere with actin will also interfere with cell division (Table 9.6). 

Monastrol Synthehc, idenhhed as cell-division inhibitor (24). Inhibits the kinesin-5 motor protein. 

Hesperadin Synthehc, identihed as cell-division inhibitor (36). Inhibits Aurora kinases. 

Lignan from Podophyllum emodi rhizomes. Also isol. from P. peltatum, other P. spp., Diphylleia grayi, Callitris drummondii and Juniperus spp. Potent cytotoxin. Cell division inhibitor. Cryst. (Me2CO aq. or MeOH). Mp 117-118°. [ajj)" —101.3° (EtOH). 4 Crystal modifications reported. Mp s up to 188-189° have been reported for carefully dried samples. 

Keywords— cell division inhibitor, Streptomyces, drug resistance, morphological change. 

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