A new candidate for an anti-HIV-1 agent: modified cyclodextrin sulfate (mCDS71)

Moriya, Tamon; Saito, K.; Kurita, Hironori; Matsumoto, Kazuo; Otake, Toru; Mori, Haruyo; Morimoto, Motoko; Ueba, Noboru; Kunita, Nobuharu

doi:10.1021/jm00063a018

Cited by 37 publications

(33 citation statements)

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“…mCDS71 was synthesized as reported by Moriya et al (1993). The 50% inhibitory concentration (IC 50 ) of mCDS71, determined as described below, for laboratory strain HIV-1 LAI on MT-4 cells was 0.77 µg/ml and the selective index (SI) was 364 when compared with the 50% cytotoxic concentration (CC 50 ).…”

Section: Compoundsmentioning

confidence: 99%

Characterization of Human Immunodeficiency Virus Type 1 Resistant to Modified Cyclodextrin Sulphate (mCDS71) in Vitro

Mori

Otake

Oishi

et al. 1999

Antivir Chem Chemother

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Drug resistance of human immunodeficiency virus type 1 (HIV) to modified cyclodextrin sulphate (mCDS71) has been analysed with respect to both the in vitro appearance of resistance to the compound and the mechanism of the acquisition of resistance. Resistant strains could be obtained in all three strains (NL432, KK-1 and A018) tested after serial passages in MT-4 cells with a gradual increase of the concentration of mCDS71. Cross-resistance both to mCDS71 and dextran sulphate 8000 was observed. As a result of sequencing analysis of the gp120 V3-C5 region of resistant strains, the mechanism of resistance can be explained in several ways: (i) substitution of sugar chain-binding amino acids, N and S; (ii) three to five amino acid deletion in V4 loop; and (iii) several mutations in V3 and V4 regions. The real cause of the resistance may be a combination of these three mechanisms. The results suggest that the target of mCDS71 is relatively widely distributed on the viral surface glycoprotein.

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Section: Compoundsmentioning

confidence: 99%

Characterization of Human Immunodeficiency Virus Type 1 Resistant to Modified Cyclodextrin Sulphate (mCDS71) in Vitro

Mori

Otake

Oishi

et al. 1999

Antivir Chem Chemother

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“…Toxicity was not observed after oral administration of mCDS11 to mice at a dose of 3 g kg-1 (Moriya et al, 1991) and at doses of 0.5 and 2 g kg-1 day ' for 5 days (Otake et al, 1994). Recently, Moriya et al (1993) reported an advanced investigation of modified CDS. A series of C-2 modified CDS were synthesized instead of C-6 modified analogues for the development of a more satisfactory oral anti-HIV agent with high activity.…”

Section: Pharmacokinetic Profilementioning

confidence: 99%

“…A series of C-2 modified CDS were synthesized instead of C-6 modified analogues for the development of a more satisfactory oral anti-HIV agent with high activity. The plasma peak level of the modified B-CDS mCDS71, determined by the anti-HIV bioassay, after oral administration to rats at 1 g kg-1 , was 0.32 mg mr" (Moriya et al, 1993). These compounds should be pursued for their potential as oral drug candidates in the prophylaxis and/or therapy of HIV infections in humans.…”

Section: Pharmacokinetic Profilementioning

confidence: 99%

“…Shortly after the identification and isolation of the virus responsible for the acquired immune deficiency syndrome (AIDS) (subsequently named the human immunodeficiency virus, HIV), several groups, following a suggestion of De Clercq (1986), demonstrated that heparin and other polysulfates are potent and selective inhibitors of HIV-1 replication in cell culture (Ito et el., 1987(Ito et el., , 1991suya et el., 1988;Mizumoto et ei., 1988;Yoshida et al, 1988;Hirabayashi et el., 1989;Jurkiewicz et el., 1989;Sugawara et al, 1989;Tochikura et al, 1989;Anand et el., 1990a,b;Kaneko et al, 1990;Montefiori et al, 1990;Weiler et al, 1990;Schols et sl., 1990aSchols et sl., , 1991Von Briesen et al, 1990;Aoki et al, 1991;Bagasra et al, 1988Bagasra et al, , 1991Sosa et al, 1991;Handa et al, 1991;Hatanaka et al, 1991;McClure et al, 1991;Moriya et al, 1991Moriya et al, , 1993Otake et al, 1991Otake et al, , 1994Witvrouw et al, 1991Witvrouw et al, , 1992Witvrouw et al, , 1994Mizuno et al, 1992;Uryu et al, 1992;Barzu et al, 1993;Beutler et al, 1993;Damonte et el., 1994). Several polysulfates were also found to be active against a wide variety of enveloped viruses (Baba et el., 1988c;De Clercq, 1990, 1993;Andrei et el., 1991;Schols et al...…”

Section: Introductionmentioning

confidence: 99%

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Antiviral Portrait Series: 4. Polysuifates as Inhibitors of HIV and Other Enveloped Viruses

Witvrouw¹,

Desmyter²,

Clercq

1994

Antivir Chem Chemother

101

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Polysulfates are highly potent and selective inhibitors of the in vitro replication of HIV and other enveloped viruses. They not only inhibit the cytopathic effect of HIV, but also prevent HIV-induced syncytium (giant cell) formation. They also act synergistically with other anti-HIV drugs. The anti-HIV activity of polysulfates is a result of their shielding of the positively charged sites in the V3 loop of the viral envelope glycoprotein gp120. When polysulfates were administered intravenously to rabbits, their half-life was approximately 2h. Although they are very poorly absorbed following oral administration, they can be made orally bioavailable with the appropriate chemical modifications. Also, polysulfates may lose (much of) their anticoagulant activity upon chemical modification without giving up their anti-HIV activity. Their efficacy in the therapy and/or prophylaxis of retroviral infections remains to be demonstrated both in animal models and in humans.

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“…Moriya et al synthesized a series of modified cyclodextrin sulfates and reported a new candidate for an anti-HIV-1 agent, mCD71 Lp-CD(2-0-CH2Ph)7(S03Na)14] ' The modified CD had higher inhibitory activity than mCDll L~-CD(6-S-CH2Ph)3(S03K)16J against HIV. CDS [~-CD(S03K)14] and DS (dextran sulfate) also have this activity, but their activity is substantially 10wer than those of mCD71 and mCDll (Moriya et al, 1993).…”

Section: Polysaccharidesmentioning

confidence: 99%

Trends in the Development of Biofunctional Saccharides in Japan.

Kobayashi

1997

FSTI

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A ra ya, Akita-shi 0/0-]6, Japan Now in Japan, healthy foodstuffs have been strongly requested, and several kinds of saccharides were developed for the purpose of cholesterol reduction, stool regulation, belly conditioning, protection from caries, bifidus factor etc.Polysaccharides, reserve saccharides such as starch, structural polysaccharides such as cellulose, hemicellulose and chitin show some biofunctional effects according with their molecular weight and structure. Especially the density and the location of branches may play an irnportant role in biofunctional effects, and the branches should be at every key point. Several kinds of oligosaccharides having 2-5 units and polysaccharides were commercialized as healthy foodstuffs. Oligosaccharides having biofunctional effects against plants and microbes were also composed of around 6 units of monosaccharide. Moreover, even monosaccharides themselves having a certain structure show some biofunctional effects.

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A new candidate for an anti-HIV-1 agent: modified cyclodextrin sulfate (mCDS71)

Cited by 37 publications

References 1 publication

Characterization of Human Immunodeficiency Virus Type 1 Resistant to Modified Cyclodextrin Sulphate (mCDS71) in Vitro

Characterization of Human Immunodeficiency Virus Type 1 Resistant to Modified Cyclodextrin Sulphate (mCDS71) in Vitro

Antiviral Portrait Series: 4. Polysuifates as Inhibitors of HIV and Other Enveloped Viruses

Trends in the Development of Biofunctional Saccharides in Japan.

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