Polyamine aza-cyclic compounds demonstrate anti-proliferative activity in vitro but fail to control tumour growth in vivo

Wong, P.E., Tetley, L., Dufès, C., Chooi, K.W., Bolton, K., Schatzlein, A.G. and Uchegbu, I.F. (2010) Polyamine aza-cyclic compounds demonstrate anti-proliferative activity in vitro but fail to control tumour growth in vivo. Journal of Pharmaceutical Sciences, 99 (11). pp. 4642-4657. 10.1002/jps.22165.

Full text not available from this repository.

DOI: 10.1002/jps.22165

Abstract

Cationic polyamines such as the poly(propylenimine) dendrimers (DAB 16) are anti-tumour agents (Dufes et al., 2005, Cancer Res 65:8079-8084). Their mechanism of action is poorly understood, but the lack of in vivo toxicity suggests cancer specificity. To explore this polyamine pharmacophore we cross-linked the aza-cyclic compound, hexacyclen, with 1,4-dibromobutane or 1,8-dibromooctane to yield the polyamines [poly(butylhexacyclen)-CL4] or [poly(octylhexacyclen)-CL8] respectively, both free of primary amines. We characterised the compounds and their respective nanoparticles and examined their interaction with the putative targets of the cationic polyamines: the cell membrane and DNA. Like DAB 16, CL4 and CL8 bind plasmid DNA and all three compounds interrupted the cell cycle of A431 epidermoid carcinoma cells in the S-phase. Additionally all three compounds disrupted erythrocyte membranes, with CL8 and DAB 16 being more active, in this respect, than CL4. CL4 (IC(50) = 775.1 mu g mL(-1)) and CL8 (IC(50) = 8.4 mu g mL(-1)), in a similar manner to DAB 16, were anti-proliferative against A431 cells; although unlike DAB 16, CL4 and CL8 were not tumouricidal against A431 xenografts in mice, indicating that primary amines may play an important role in the in vivo activity of DAB 16

Item Type:Article
Uncontrolled Keywords:polyamines; aza-cyclic compounds; cytotoxicity; cancer; poly(propylenimine) dendrimers; DAB 16; DNA binding
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:2311
Journal or Publication Title:Journal of Pharmaceutical Sciences
Deposited By:Library Staff
Deposited On:07 Oct 2011 17:25
Last Modified:07 Oct 2011 17:25

Repository Staff Only: Item control page

School of Pharmacy Staff Only: Edit a copy to replace this item