Synthetic Polyelectrolytes as Tumour Inhibitors

Carbetimer, a new synthetic low molecular weight polyelectrolyte with a novel structure displayed antitumor activity in a number of animal tumor model systems and in vitro investigations. Based on these findings it was brought to a phase I clinical trial in patients with advanced malignant disease after failure of conventional treatment or with no conventional treatment available. Forty-eight patients received 98 courses. The schedule was a one hour i.v. infusion every four weeks. The starting dose was 180 mg/m2 and dose escalation was performed according to a modified Fibonacci formula up to 16,690 mg/m2. At least three patients were treated at each dose level and each patient was eligible to receive repeat courses at the same dose, until progressive disease or dose-limiting toxicity intervened. No hematological toxicity was encountered. Some adverse effects such as reversible proteinuria, hypercalcaemia, pain at infusion site, nausea and vomiting and fatigue were seen partly in a dose-related manner but did not represent the maximum tolerated dose (MTD). The limiting toxicity at the highest dose level of 16,690 mg/m2 consisted of ocular symptoms ('light flashes') accompanied by a modest decrease of blood pressure and nausea or vomiting during a one hour infusion. 16,690 mg/m2/1 hour was considered the MTD. There were four deaths on study, all considered disease-related. Fourteen patients had stable disease for more than two courses, which, however, could also be explained by the natural course of disease. No clear-cut antitumor responses were noted in our study center. The recommended dose for phase II trials derived from our results is 12,550 mg/m2/2 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Antineoplastic activity of synthetic polyelectrolytes was first demonstrated by Regelson et al [1,2].…”

Section: Introductionmentioning

confidence: 99%

Phase I trial of the polyelectrolyte carbetimer administered i.v. once every four weeks

et al. 1988

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“…The charge density and solution configuration of these polymers were varied over a wide range by the proper choice of substituents on the backbone of the molecule and substitutions on the carboxyl groups. 10 In the AA and MA copolymer, functional groups are attached to immediately adjacent carbon atoms of the carbon backbone atoms separated by a methylene unit. These properties of the polyanionic polymers are different from the other types of polymers by means of the ionic strength as well as charge density.…”

Section: Table II Hydrogen-bonding Effect On Glass-transition Temperamentioning

confidence: 99%

“…9 The synthetic carboxylic acid polymers were first investigated as poly(acrylic acid), poly(methacrylic acid), poly(ethylene-co-maleic anhydride), and oxidized polysaccharides. 10 Among these polymers, the hydrolyzed form of divinyl ether maleic anhydride copolymer (DIVEMA, also called pyran copolymer), which contains carboxylic acid groups, exhibits high antitumor activity together with toxic side effects. 11 The aim of the study was to obtain new biologically active polymers using anhydride-containing monomers.…”

Section: Introductionmentioning

confidence: 99%

“…They induce interferon; modify the reticuloendothedial system; and display immunoadvujant, antiviral, and antitumor activity 9. The synthetic carboxylic acid polymers were first investigated as poly(acrylic acid), poly(methacrylic acid), poly(ethylene‐ co ‐maleic anhydride), and oxidized polysaccharides 10. Among these polymers, the hydrolyzed form of divinyl ether maleic anhydride copolymer (DIVEMA, also called pyran copolymer), which contains carboxylic acid groups, exhibits high antitumor activity together with toxic side effects 11…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, characterization, and antitumor activity of poly(maleic anhydride‐co‐vinyl acetate‐co‐acrylic acid)

Can

Doğan

Rzaev

et al. 2006

J of Applied Polymer Sci

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ABSTRACT:The ternary copolymerization of maleic anhydride (MA), vinyl acetate (VA), and acrylic acid (AA) [P(MA-co-VA-co-AA)], which is considered to be an acceptor-donor-acceptor system, was carried out in 1,4-dioxane with benzoyl peroxide as an initiator at 70°C under a nitrogen atmosphere. Constants of complex formation for the monomer systems in the study were determined by UVvisible (hydrogen-bonding complex) and 1 H-NMR (charge transfer complex) methods, respectively. The results show that polymerization of the P(MA-co-VA-co-AA) system proceeds by an alternating terpolymerization mechanism. It is shown that the synthesized copolymers have typical polyelectrolyte behavior, ability for reversible hydrolysis-anhydrization reactions, and semicrystalline structures. In these cases, including radical polymerization, and formation of semicrystalline structures, the hydrogen-bonding effect plays a significant role. The in vitro cytotoxicities of the synthesized terpolymer and alternating copolymer were evaluated using Raji cells (human Burkitt lymphoma cell line). The antitumor activities of prepared anion-active copolymers were studied using methyl-thiazol-tetrazolium colorimetric assay and 50% of the cytotoxic dose of each copolymer and terpolymer were calculated. Hydrolyzed P(MA-co-VA-co-AA) and P(MA-alt-AA) copolymers have sufficiently high antitumor activity, which depends on the amount of hydrogen-bonding carboxylic groups and their regular distribution in the side chain of functional macromolecules.

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“…It has been reported that the copolymer of divinyl ether with maleic anhydride (DIVEMA) has not only broad biological activities such as antitumour, antiviral, antibacterial, interferon‐inducing, and antifungal activities,1–3 but also toxic side‐effects such as enlarged liver and spleen 4. 5 Subsequently, many attempts were made to reduce the toxic side‐effects 6–12.…”

Section: Introductionmentioning

confidence: 99%

Syntheses, antitumour activities and antiangiogenesis of 1,2,3‐tris(ethoxycarbonyl)‐2‐propyl acrylate and its polymers

Kim

Chung

Lee

et al. 2001

Polymer International

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A new monomer, 1,2,3‐tris(ethoxycarbonyl)‐2‐propyl acrylate (TPA), was synthesized by reaction of acryloyl chloride and triethyl citrate. The homopolymer of TPA and its copolymers with acrylic acid (AA), vinyl acetate (VAc) and maleic anhydride (MAH) were prepared by polymerization using lauroyl peroxide (LPO) at 70 °C for 24 h. The structures of TPA and its polymers were identified by FTIR, 1H NMR, 13C NMR spectroscopies, and elemental analysis. The number average molecular weights and polydispersity indices of the synthesized polymers determined by GPC were in the range 4200–23 000 g mol−1 and 1.1–2.1, respectively. The IC50 values of the synthesized samples against cancer cell lines were greater than those of 5‐fluorouracil (5‐FU). The percentage inhibition values of SV40 DNA replication were 82.2 for TPA, 34.3 for poly (TPA), 81.9 for poly(TPA‐co‐AA), 82.0 for poly(TPA‐co‐VAc), 35.6 for poly(TPA‐co‐MAH) and 12.7 for 5‐FU. The inhibitions of SV40 DNA replication and antiangiogenesis for the synthesized TPA and its polymers are much greater than those of the control. © 2001 Society of Chemical Industry

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Synthetic Polyelectrolytes as Tumour Inhibitors

Cited by 38 publications

References 4 publications

Phase I trial of the polyelectrolyte carbetimer administered i.v. once every four weeks

Phase I trial of the polyelectrolyte carbetimer administered i.v. once every four weeks

Synthesis, characterization, and antitumor activity of poly(maleic anhydride‐co‐vinyl acetate‐co‐acrylic acid)

Syntheses, antitumour activities and antiangiogenesis of 1,2,3‐tris(ethoxycarbonyl)‐2‐propyl acrylate and its polymers

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