Delcros, Jean-Guy published the artcileEffect of Spermine Conjugation on the Cytotoxicity and Cellular Transport of Acridine, Computed Properties of 87905-98-4, the main research area is acridine spermidine conjugate preparation transport antitumor.
Polyamines are believed to be potent vectors for the selective delivery of chemotherapeutic agents into cancer cells. In this paper, we report the effect of spermine conjugation on the cytotoxic and transport properties of acridine. Six derivatives, composed of a spermine chain attached at its N1 position to an acridine via an aliphatic chain, were synthesized. The aliphatic linker, comprised of 3-5 methylene units, was connected to the position-9 of the heterocycle through either an amide or an amine linkage. Independently of their architecture, all ligands showed a high affinity for DNA binding but a limited DNA sequence selectivity. In a whole cell assay with L1210 and Chinese hamster ovary (CHO) cells, the aminoacridines (IC50 values around 2 μM) were more potent than the amidoacridines (IC50 values between 20 and 40 μM). This was related to a less efficient transport for the latter. As determined from competitive uptake studies with [14C]spermidine, all conjugates had a high affinity for the polyamine transport system (PTS). However, on the basis of competitive studies with an excess of spermidine and on the differential effect on cell growth and accumulation in CHO and in the mutant PTS deficient CHO-MG cells, the accumulation of the conjugates through the PTS was poor but still more efficient for the aminoacridines. α-Difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, which induces an up-regulation of the activity of the PTS, enhanced accumulation of all acridine conjugates through the PTS and had a synergistic effect on the potency of the acridine conjugates to inhibit cell growth. Despite their high affinity for the PTS, the low amount of derivatives transiting through the PTS is likely to be related to their ability to repress rapidly and efficiently the activity of the PTS and, consequently, to inhibit their own uptake via this system.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 87905-98-4 belongs to class alcohols-buliding-blocks, name is Benzyl (5-hydroxypentyl)carbamate, and the molecular formula is C13H19NO3, Computed Properties of 87905-98-4.
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